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The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane ( PU2M ) with aryl boronic ester-based diol ( M2 ) moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza- s -indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by 1 H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both L. donovani and L. major intracellular amastigote burden compared to the free AmB. Overall, this work illustrated a promising therapeutic application of dual endogenous stimuli-triggered degradable theranostic polyurethane for target-specific drug delivery of AmB, to mitigate leishmaniasis.

In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from inflammatory microenvironments. Macrophages infiltrate and polarize toward a pro-inflammatory phenotype (M 1 -like), thereby increasing the severity of inflammation. Therefore, we aimed to suppress the pro-inflammatory activity of M 1 -like macrophages and decrease their infiltration at the site of inflammatory insult to resolve tissue inflammation. To achieve this, we developed a theranostic curcumin-loaded nanoemulsion platform that delivers a low dose of curcumin, a known anti-inflammatory phytochemical, to macrophages and allows in vivo tracking of macrophages by near-infrared fluorescence (NIRF) imaging technique. In vitro, we showed that curcumin-loaded nanoemulsion suppressed polarization of macrophages towards M 1 -like phenotype, consequently decreasing the release of pro-inflammatory cytokines and mediators like IL-6, IL-[Formula: see text] TNF-[Formula: see text], and nitric oxide (NO). Furthermore, curcumin-loaded nanoemulsion increased the level of IL-10, an anti-inflammatory cytokine, and protected macrophages against ferroptosis compared to drug-free nanoemulsion. In a rodent model of Complete Freund's adjuvant (CFA)-induced inflammation, we demonstrated that infiltrating macrophages sequestered curcumin-loaded nanoemulsion droplets and acted as cellular drug depots at the site of inflammation. This consequently decreased macrophage infiltration at the CFA-induced inflammation site in both sexes compared to drug-free nanoemulsion, as demonstrated by NIRF imaging, H&E staining, and immunofluorescence. Taken together, our results indicated that the anti-inflammatory efficacy of curcumin was significantly improved when directly delivered to pro-inflammatory macrophages via theranostic nanoemulsion. This work opens an avenue for exploring theranostic nanoemulsions as a platform for delivering natural anti-inflammatory products for immune modulation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Nanocarriers have shown significant promise in the diagnosis and treatment of various diseases, utilizing a wide range of biocompatible materials such as metals, inorganic substances, and organic components. Despite diverse design strategies, key physicochemical properties, including hydrodynamic diameter, shape, surface charge, and hydrophilicity/lipophilicity, are crucial for optimizing biodistribution, pharmacokinetics, and therapeutic efficacy. However, these properties are often influenced by drug payload, presenting an ongoing challenge in developing versatile platform technologies for theranostics. To enable tissue- and organ-specific targeting while minimizing nonspecific uptake, renal clearable Harvard dots (H-dots) have emerged as a promising organic nanocarrier platform. Composed of an ε-polylysine backbone for a tunable charge, near-infrared fluorophores for tracking their fate in living organisms, and β-cyclodextrins for potential drug delivery, H-dots offer a multifunctional approach to theranostic nanomedicine. Recent studies demonstrate that H-dots are effective for targeted imaging and drug delivery to solid tumors. This review highlights current nanocarrier design strategies and recent advances in H-dot applications for cancer diagnosis and therapy.

Colorectal cancer (CRC) is a serious public health concern worldwide. Immune checkpoint inhibition medication is likely to remain a crucial part of CRC clinical management. This study aims to create new super paramagnetic iron oxide nano-carrier (SPION) that can effectively transport miRNA to specific CRC cell lines. In addition, evaluate the efficiency of this nano-formulation as a therapeutic candidate for CRC. Bioinformatics tools were used to select a promising tumor suppressor miRNA (mir-497-5p). Green route, using Fusarium oxyporium fungal species, manipulated for the synthesis of SPION@Ag@Cs nanocomposite as a carrier of miR-497-5p. That specifically targets the suppression of PD1/PDL1 and CTLA4pathways for colorectal therapy. UV/visible and FTIR spectroscopy, Zeta potential and MTT were used to confirm the allocation of the miR-497 on SPION@Ag@Cs and its cytotoxicity against CRC cell lines. Immunofluorescence was employed to confirm transfection of cells with miR-497@NPs, and the down- regulation of CTLA4 in HT29, and Caco2 cell lines. On the other hand, PDL1 showed a significant increase in colorectal cell lines (HT-29 and Caco-2) in response to mir497-5p@Nano treatment. The data suggest that the mir-497 -loaded SPION@Ag@Cs nano-formulation could be a good candidate for the suppression of CTLA4in CRC human cell lines. Consequently, the targeting miR-497/CTLA4 axis is a potential immunotherapy treatment strategy for CRC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The limited and backward diagnostic approaches elicit high mortality associated with pulmonary fibrosis (PF) because they fail to identify injury phase of PF. Developing a precisely theranostic nanoplatform presents a promising shortcut to reverse PF. Herein, a specific molecular nanotheranostic (Casp-GNMT), which is triggered by endogenous cysteinyl aspartate specific proteinase-3 (caspase-3), boosts antifibrotic efficacy through bioimaging synergistic with chemotherapy at molecular level, facilitating by ionizable lipid and reactive oxygen species sensitive lipid for precise and manageable therapy. The activation of molecular imaging probe (pCY-pairs) by consumption of endogenous caspase-3 initiates fluorescence resonance energy transfer-guided theranostic pattern, aiming to restore mitochondrial dysfunction-induced oxidative stress and inflammatory responses in alveolar epithelial cells II (AECs II). This process sequentially resists the expression of interleukin-1β and vascular endothelial growth factor receptor through combined with nintedanib, further suppressing abnormal injury of AECs II and persistent migration and proliferation of inflammatory cells. Especially, the homeostasis of injured AECs II diminishes excessive accumulation of transforming growth factor-β to restrain myofibroblasts proliferation and collagen deposition, thereby amplifying the possibility of reversing PF. This theranostic nanoplatform is proposed to provide a prompt and exact approach to enhance diagnostic authenticity and treating efficiency through harnessing endogenous indicator for PF reversal., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed via attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction. Nano-sized (∼160 nm) spherical DOX/IPD-loaded RHLs with a narrow size distribution and negative zeta potential were successfully fabricated. The RHLs demonstrated enhanced cellular uptake of DOX in SCCVII cells compared to conventional radiopaque liposomes, likely due to clathrin-mediated endocytosis. Additionally, pH-dependent DOX release and reduced IPD leakage were observed. In vivo studies using SCCVII tumor-xenografted mice showed that RHLs exhibited improved CT contrast efficiency and anti-tumor efficacy, along with systemic biocompatibility, attributed to enhanced tumor-targeting properties. These findings suggest that the RHL system could serve as a promising nano-platform for tumor theranostics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging because of its depth, which often leads to misdiagnosis during ultrasound examinations. The unique PDAC tumor microenvironment (TME) is characterized by significant fibrous tissue growth, and high interstitial pressure hinders drug penetration into tumors. Additionally, hypoxia and immune suppression within the tumor contribute to poor responses to radiotherapy and chemotherapy, ultimately leading to an unfavorable prognosis. In this study, aPD-L1-modified docetaxel and perfluoropentane-loaded liquid‒vapor phase-transformation lipid nanoparticles (aPDL1-DTX/PFP@Lipid) were synthesized and had an average diameter of 61.63 nm with 84.3% antibody modification. We demonstrated that the nanoparticles (NPs) exhibited excellent PDAC-targeting capabilities both in vitro and in vivo. Upon exposure to low-intensity pulsed ultrasound (LIPUS) stimulation, the NPs underwent a phase transformation to form microbubbles with substantial molecular ultrasound diagnostic effects, and combined treatment resulted in a tumor growth inhibition rate of 88.91%. This treatment strategy also led to the infiltration of CD8 + T cells, the downregulation of Treg cells, the promotion of M1 macrophage polarization, the inhibition of fibrosis to reduce tumor stromal pressure, and the facilitation of perfluoropentane (PFP) gasification to release O 2 and improve tumor hypoxia. In conclusion, aPD-L1-modified liquid‒vapor phase-transformation nanoparticles loaded with docetaxel (DTX) and PFP were successfully combined with ultrasound for the molecular diagnosis and targeted treatment of PDAC. aPDL1-DTX/PFP@Lipid could reshape the PDAC TME, offering a new approach for ultrasound-mediated diagnosis and treatment with promising clinical applications., Competing Interests: Declarations. Ethics approval and consent to participate: Animal care was performed in accordance with institutional institution guidelines. All animal studies were approved by the Animal Ethical Committee of Fujian Medical University (grant No. IACUC FJMU 2022 − 0721). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Outer membrane vesicles (OMVs) derived from Gram-negative bacteria naturally serve as a heterologous nano-engineering platform, functioning as effective multi-use nanovesicles for diagnostics, vaccines, and treatments against pathogens. To apply refined OMVs for human theranostic applications, we developed naturally exposed receptor-binding domain (RBD) OMVs grafted with antigen 43 as a minimal modular system targeting angiotensin-converting enzyme 2 (ACE2)., Methods: We constructed E. coli -derived OMVs using the antigen 43 autotransporter system to display RBD referred to as viral mimetic Ag43β700_RBD OMVs. Based on this, Ag43β700_RBD protein were expressed onto Escherichia coli ( E. coli ) membrane. Artificial viral mimetic Ag43β700_RBD OMVs were fabricated by self-assembly through membrane disruption of the Ag43β700_RBD E. coli using a chemical detergent mainly containing lysozyme. Through serial centrifugation to purify fabricated OMVs, spherical Ag43β700_RBD OMVs with an average diameter of 218 nm were obtained. The confirmation of the RBD expressed on OMVs was performed using trypsin treatment., Results: Our viral mimetic Ag43β700_RBD OMVs had an impact on the theranostic studies: (i) angiotensin-converting enzyme 2 blockade assay, (ii) enzyme-linked immunosorbent assay for the OMVs, and (iii) intracellular uptake and neutralization assay. As serodiagnostic surrogates, Ag43β700_RBD OMVs were applied to ACE2 blockade and OMVs-ELISA assay to quantify neutralization antibodies (nAbs). They reduced the robust immune response in vitro, especially IL-6 and IL-1β. Experiments in mice, Ag43β700_RBD OMVs was successfully proven to be safe and effective; they produced a detectable level of nAbs with 39-58% neutralisation and reduced viral titres in the lungs and brain without weight loss., Conclusion: The developed viral mimetic Ag43β700_RBD OMVs may therefore be applied as a nanovesicle-theranostic platform for further emerging infectious disease-related diagnosis, vaccination, and treatment., Competing Interests: The authors declare that they have no competing interests in this work., (© 2025 Ahn et al.)

In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system's applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach. A novel esterase-activated EPR strategy prodrug, OBHSA-PEG-DCM, was designed. This prodrug links OBHSA, a protein degrader capable of efficient ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4 H -pyran, DCM) via an ester bond. This integration facilitates targeted drug delivery and enhances the retention of the fluorescent group within the tumor, allowing distinct in vivo tumor imaging periods. Experimental results show that, benefiting from overexpressed esterase in cancer cells, OBHSA-PEG-DCM can be efficiently hydrolyzed, releasing OBHSA and pegylated DCM. OBHSA demonstrated potent inhibition against MCF-7 cells (IC 50 = 1.09 μM). Simultaneously, pegylated DCM exhibited remarkable in vivo imaging capabilities, lasting up to 12 days in mice, due to the enhanced permeability and retention (EPR) effect. OBHSA-PEG-DCM holds promise as a theranostic agent for ERα-positive breast cancer, offering both therapeutic and diagnostic capabilities. Importantly, this study highlights the utility of pegylated NIR fluorophores for long-circulating drug delivery systems, addressing current challenges in achieving high-contrast tumor imaging and effective targeted drug release.

With the growing demand for precision medicine and advancements in microneedle technology, microneedle-based drug delivery systems have evolved into integrated theranostic platforms. However, the development of these systems is currently limited by the absence of clear conclusions and standardized construction strategies. The end-to-end concept offers an innovative approach to theranostic systems by creating a seamless process that integrates target sampling, sensing, analysis, and on-demand drug delivery. This approach optimizes each step based on data from the others, effectively eliminating the traditional separation between drug delivery and disease monitoring. Furthermore, by incorporating artificial intelligence and machine learning, these systems can enhance reliability and efficiency in disease management, paving the way for more personalized and effective healthcare solutions. Based on the concept of end-to-end and recent advancements in theranostic systems, nanomaterials, electronic components, micro-composites, and data science, we propose a modular strategy for constructing integrated microneedle-based theranostic systems by detailing the methods and functions of each critical component, including monitoring, decision-making, and on-demand drug delivery units, though the total number of units might vary depending on the specific application. Notably, decision-making units are emerging trends for fully automatic and seamless systems and featured for integrated microneedle-based theranostic systems, which serve as a bridge of real-time monitoring, on-demand drug delivery, advanced electronic engineering, and data science for personalized disease management and remote medical application. Additionally, we discuss the challenges and prospects of integrated microneedle-based theranostic systems for precision medicine and clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prostate-Specific Membrane Antigen (PSMA) is a highly expressed and structurally unique target specific to prostate cancer (PCa). Diagnostic and therapeutic approaches in nuclear medicine, coupling PSMA ligands with radionuclides, have shown significant clinical success. PSMA-PET/CT effectively identifies tumors and metastatic lymph nodes for imaging purposes, while 177Lu -PSMA-617 (Pluvicto) has received FDA approval for treating metastatic castration-resistant PCa (mCRPC). Despite their success, radionuclide-based diagnostic and therapeutic methods face limitations such as high costs and significant side effects. Recently, near-infrared (NIR) fluorescence imaging and phototherapy have advanced significantly in biomedical applications. It's benefits, such as deep tissue penetration, real-time precision, and minimal side effects, have driven broader clinical adoption, especially in fluorescence-guided surgery (FGS). This review suggests combining NIR dyes with PSMA ligands to enable targeted, high-resolution imaging with superior signal-to-background ratios, facilitating precise FGS. NIR techniques can also aid pathological diagnosis in ex vivo specimens. Furthermore, combining photosensitizers with PSMA ligands allows localized photothermal (PTT) or photodynamic therapy (PDT) under NIR irradiation, producing heat or reactive oxygen species (ROS) to treat PCa. This review aims to extend the clinical success of radionuclide-based PSMA targeting by exploring advances in NIR-based FGS and phototherapy, presenting a promising new diagnostic and therapeutic approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Jiang, Kadeerhan, Zhang, Guo, Guo and Wang.)

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction 10 B (n, alpha) 7 Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, "AB-type" Lactosome ® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o -Carborane (Carb) or 1,2-dihexyl- o -Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the "molecular glue" effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either 10 B-Carb or 10 B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any 10 B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with 10 B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., "theranostics".

Integration of different therapeutic performances into one platform is an innovative development for using multiple applications in real-time. In this paper, for the first time we exploited the concurrent capacity of radio and photosensitizing in a theranostic nanoMOFs based on bismuth, zirconium, and porphyrin. The porosity of nanoMOFs provided the capability of doxorubicin loading and chemotherapy besides enhanced photodynamic and radiation therapy (PDT & RT). Its PEGylation and aptamer (MUC1) immobilization endowed the platform with high biocompatibility and targeted tumor killing, respectively. In vitro assay exhibited that this aptamer immobilized DOX-loaded PEGylated MOF (Apt@DOX) produced more toxicity against 4 T1 cells compared to non-targeted nanoparticles (NP@DOX), especially when the treatment combined with PDT or/and RT. In vivo experiment also provided great results for tumor growth, survival rate, and body weight for 4 T1 bearing mice injected by Apt@DOX in combination with irradiation by 660 nm laser and/or exposure to 3 Gy dosage of X-ray radiation. The CT imaging of injected mice with targeted and non-targeted bismuth-based MOF introduced this nanoplatform as a promising CT contrast agent. Resultantly, we can present our as-synthesized nanoplatform as an efficient multifunctional theranostics with the ability of multimodal therapy and diagnostic performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen ( 1 O 2 ) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O 2 1 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Skin injuries caused by physical, pathological, and chemical factors not only compromise appearance and barrier function but can also lead to life-threatening microbial infections, posing significant challenges for patients and healthcare systems. Artificial intelligence (AI) technology has demonstrated substantial advantages in processing and analyzing image information. Recently, AI-based methods and algorithms, including machine learning, deep learning, and neural networks, have been extensively explored in wound care and research, providing effective clinical decision support for wound diagnosis, treatment, prognosis, and rehabilitation. However, challenges remain in achieving a closed-loop care system for the comprehensive application of AI in wound management, encompassing wound diagnosis, monitoring, and treatment. This review comprehensively summarizes recent advancements in AI applications in wound repair. Specifically, it discusses AI's role in injury type classification, wound measurement (including area and depth), wound tissue type classification, wound monitoring and prediction, and personalized treatment. Additionally, the review addresses the challenges and limitations AI faces in wound management. Finally, recommendations for the application of AI in wound repair are proposed, along with an outlook on future research directions, aiming to provide scientific evidence and technological support for further advancements in AI-driven wound repair theranostics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Vulnerable plaques, which are high-risk features of atherosclerosis, constitute critical elements in the disease's progression due to their formation and rupture. Macrophages and macrophage-derived foam cells are pivotal in inducing vulnerability within atherosclerotic plaques. Thus, understanding macrophage contributions to vulnerable plaques is essential for advancing the comprehension of atherosclerosis and devising novel therapeutic and diagnostic strategies. This review provides an overview of the pathological characteristics of vulnerable plaques, emphasizes macrophages' critical role, and discusses advanced strategies for their diagnosis and treatment. It aims to present a comprehensive macrophage-centered perspective for addressing vulnerable plaques in atherosclerosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cyclometalated iridium(III) complexes have emerged as versatile candidates for cancer theranostics, offering integrated diagnostic imaging and potent singlet oxygen ( 1 O 2 ) generation for photodynamic therapy (PDT). However, their application has been limited by subdued photoluminescence, primarily due to intramolecular motion-induced excited energy dissipation. In this study, we address these limitations through the design and synthesis of five novel iridium(III) complexes: IrC2, IrC4, IrC6, IrC8, and IrC12. Our approach employs meticulous side-chain extending strategy to modulate side-chain length, thereby reducing intramolecular motion and significantly enhancing both one- and three-photon emissions and 1 O 2 production in the aggregated state. Detailed photophysical investigations, supported by crystallographic insights, reveal that side-chain elongation substantially amplifies these properties. Among the synthesized complexes, IrC8 stands out as a superior candidate for image-guided photodynamic therapy in cellular and 3D tumor spheroid models. This investigation pioneers the simultaneous enhancement of dual-photon emissions and PDT efficacy through a novel side-chain extension strategy in iridium(III) complexes, paving the way for their translational application in clinical theranostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oral Squamous Cell Carcinoma (OSCC) is a widespread and challenging disease that accounts for 94% of cancers of the oral cavity worldwide. Bacteriophages (phages) have shown promise as a potential theranostic agent for the treatment of OSCC. It may offer advantages in overcoming the challenges of conventional methods. Modern high-throughput pyrosequencing techniques confirm the presence of specific bacterial strains associated with OSCC. Bio-panning and filamentous phages facilitate visualization of the peptide on surfaces and show high affinity in OSCC cells. The peptide has the potential to bind integrin (αvβ6), aid in diagnosis, and inhibit the proliferation of OSCC cells. Mimotopes of tumor-associated antigens show cytotoxic and immune responses against cancer cells. Biomarker-based approaches such as transferrin enable early OSCC diagnosis. A modified temperate phage introduces CRISPR-Cas3 to target antimicrobial-resistant bacteria associated with OSCC. The research findings highlight the evolving field of phage diagnostics and therapy and represent a new avenue for non-invasive, targeted approaches to the detection and treatment of OSCC. However, extensive clinical research is required to validate the efficacy of phages in innovative cancer theranostic strategies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Carbon dots (CDs) with intrinsic bioactivities are candidates for bioimaging and disease therapy due to their diverse bioactivities, high biocompatibility, and multiple functionalities in multimodal theranostics. It is a multidisciplinary research hotspot that includes biology, physics, materials science, and chemistry. This progress report discusses the CDs with intrinsic bioactivities and their applications in multimodal theranostics. The relationship between the synthesis and structure of CDs is summarized and analyzed from a material and chemical perspective. The bioactivities of CDs including anti-tumor, antibacterial, anti-inflammatory etc. are discussed from biological points of view. Subsequently, the optical and electronic properties of CDs that can be applied in the biomedical field are summarized from a physical perspective. Based on the functional review of CDs, their applications in the biomedical field are reviewed, including optical diagnosis and treatment, biological activity, etc. Unlike previous reviews, this review combines multiple disciplines to gain a more comprehensive understanding of the mechanisms, functions, and applications of CDs with intrinsic bioactivities., (© 2024 Wiley‐VCH GmbH.)

Gold nanorods (AuNRs) are important photothermal therapeutic agents; however, a single therapy does not achieve satisfactory outcomes, and the synthesis process often leads to the adsorption of cetyltrimethylammonium bromide on the surface of AuNRs, which reduces its biocompatibility. Natural polyphenols are abundant in natural plants and have good biocompatibility. The metal-polyphenol network is formed by the coordination of metal ions and polyphenols, which has good drug loading, surface adhesion, and biocompatibility. In this study, the metal-polyphenol network structure formed by a transition metal (iron) and natural polyphenol tannic acid was used to modify the surface of gold nanorods (AuNRs@TF). Additionally, the surfaces of AuNRs were modified using the targeted functional molecule mercapto folic acid (AuNRs@TFF). The constructed composite nanomaterials AuNRs@TFF has good biocompatibility and tumor targeting ability. Tannic acid‑iron degrades in the tumor microenvironment and releases iron ions that catalyze the Fenton reaction, thereby facilitating chemodynamic therapy. The good photo-thermal ability of AuNRs generate good photoacoustic signals to facilitate photoacoustic imaging mediation and enhances photothermal and chemodynamic therapy performance. This study expands on the application of AuNRs in the field of nanomedicine. The simple and effective design of AuNRs@TFF provides a strategy for the development of synergistic therapeutic agents for photothermal therapy and chemodynamic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Kidney diseases are characterized by their intricate nature and complexity, posing significant challenges in their treatment and diagnosis. Nanoparticles (NPs), which can be further classified as synthetic and biomimetic NPs, have emerged as promising candidates for treating various diseases. In recent years, the development of engineered nanotherapeutics has focused on targeting damaged tissues and serving as drug delivery vehicles. Additionally, these NPs have shown superior sensitivity and specificity in diagnosis and imaging, thus providing valuable insights for the early detection of diseases. This review aims to focus on the application of engineered synthetic and biomimetic NPs in kidney diseases in the aspects of treatment, diagnosis, and imaging. Notably, the current perspectives and challenges are evaluated, which provide inspiration for future research directions, and encourage the clinical application of NPs in this field., (© 2024 Wiley‐VCH GmbH.)

Treating all people with Cystic Fibrosis (pwCF) to the level of benefit achieved by highly efficient CFTR modulator therapies (HEMT) remains a significant challenge. Theratyping and theranostics are two distinct approaches to advance CF treatment. Both theratyping in cell lines and pwCF-derived biomaterials theranostics have unique strengths and limitations in the context of studying and treating CF. The challenges, advantages and disadvantages of both approaches are discussed here. While theratyping in cell lines offers ease of use, cost-effectiveness, and standardized platforms for experimentation, it misses physiological relevance and patient-specificity. Theranostics, on the other hand, provides a more human-relevant model for personalized medicine approaches but requires specialized expertise, resources, and access to patient samples. Integrating these two approaches in parallel and leveraging their respective strengths may enhance our understanding of CF and facilitate the development of more effective therapies for all pwCF., Competing Interests: Declaration of competing interest MDA serves as member of the Scientific Advisory Board of Fair Therapeutics Foundation, with no financial compensation. In the past MDA received personal fees from Vertex Pharmaceuticals, PTC Pharmaceuticals and Gilead Sciences, Inc. to give scientific seminars; research grants from Gilead Génese Programme, Vertex Pharmaceuticals and Proteostasis Therapeutics, Inc.; and was a previous member of Scientific Advisory Board of Vertex Pharmaceuticals and Translate Bio. IP declares that she has no other financial nor personal relationships with other people or organizations that could inappropriately influence her work., (Copyright © 2024. Published by Elsevier B.V.)

Phototheranostics integrates light-based diagnostic techniques with therapeutic interventions, offering a non-invasive, precise, and swift approach for both disease detection and treatment. The efficacy of this approach hinges on the multimodal imaging potential and photothermal conversion efficiency (PCE) of phototheranostic agents (PTAs). Despite the promise, crafting multifunctional phototheranostic organic small molecules brims with challenges. In this research, four innovative xanthene-derived PTAs are synthesized by fine-tuning the donor-π-acceptor (D-π-A) system to strike a balance between radiative and nonradiative decay. The inherent robust photostability and intense fluorescence of the traditional xanthene core are preserved, meanwhile the addition of highly electron-withdrawing groups boosts the non-radiative decay rate to enhance PCE and photoacoustic imaging capabilities. Remarkably, one of the PTAs, DMBA, demonstrates an exceptional absolute fluorescence quantum yield of 2.46% in PBS, and when encapsulated into nanoparticles, it achieves a high PCE of 79.5%. Consequently, DMBA nanoparticles (DMBA-NPs) are effectively employed in fluorescence, 3D photoacoustic, and photothermal imaging-guiding tumor photothermal therapy. This represents the first instance of a multimodal phototheranostic xanthene agent achieving synergistic fluorescence and photoacoustic imaging for diagnostic purposes. Furthermore, this work paves the way for leveraging xanthene fluorophores as versatile tools in the development of multifunctional reagents., (© 2024 Wiley‐VCH GmbH.)

To a certain extent, theranostic nanoplatforms promote tumor treatment efficiency. However, timely monitoring of the critical stages and signal sustainability of the entire process is challenging. In this study, multi-chambered core/shell magnetic nanoparticles (MC-MNPs) as drug and imaging agent multi-loaded nanocarriers with a synergistic release function are reported. Supraparticles with stable chambers are formed by the supercooling self-assembly of several core/shell magnetic nanoparticles composed of amphiphilic copolymers as the core and hydrophilic magnetic iron oxide nanoparticles as the shell. Desalinized doxorubicin and coumarin 6 are stored in different cavities of nanocarriers, and chitosan is used as an outer encapsulation layer. Based on their construction properties, MC-MNPs can exhibit gradient-degraded and steady-released controllability in the tumor environment. Furthermore, real-time accumulation situations and full-time diagnostic signals of nanocarriers are thoroughly demonstrated using fluorescence imaging and T 2 -weighted magnetic resonance imaging before and after magnetic hyperthermia in targeted tumors under an alternating magnetic field. Thus, MC-MNPs as theranostic nanocarriers exhibit great potential for the timely monitoring and full-time guidance of tumor treatment., (© 2024 Wiley‐VCH GmbH.)

To address the issue of high-dose treatment agents in magnetic hyperthermia-mediated multi-model tumor therapy, a unique iron-based theranostic nanoenzyme with excellent magnetothermal and catalytic properties was constructed. By using a high-temperature arc method, the iron carbon nanoparticles (MF1-3) with a particle size between 13.7 and 27.6 nm and shell thickness between 1 and 5 nm were prepared. After screening, we selected MF3 as the magnetic core due to its high Ms. value and excellent thermal properties. Under the magneto-photo dual thermal conditions, MF3 exhibited a remarkable specific absorption rate (SAR) of 4917 W/g, which was 20 times more than that of iron oxide. Notably, MF3 also exhibited best peroxidase (POD)-like catalytic in pH 5.0 and maintained stable catalytic performance at 45 °C. Considering the "starvation" strategy of cutting off the energy supply to tumor cells and killing them, the glucose oxidase (GOX) and chitosan oligosaccharide (COS) was further grafted onto MF3, forming the MF3/GOX/COS. This multifunctional therapeutic nanoenzyme not only exhibited significant peroxidase-like activity, but also had glucose decomposition and glutathione (GSH) consumption capabilities. The thermal effect significantly promoted the uptake of MF3/GOX/COS by 4T1 cells, and the IC 50 value of MF3/GOX/COS reached low to 3.75 μg/mL. In vivo anti-tumor experiment, compared with single treatment methods, the combined therapy of MF3/GOX/COS mediated magneto-photo thermotherapy (M-PTT) and starvation therapy (ST) exhibited higher tumor inhibition rate of 82.1 % by increased cell apoptosis through the mitochondrial pathway. Overall, MF3/GOX/COS therapeutic nanoenzyme combined the advantages of nano-catalysis, M-PTT and ST, providing a solution for achieving sustained, stable, and effective tumor inhibition rates at lower dose levels., Competing Interests: Declaration of competing interest We have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer is the leading cause of women's deaths and associated comorbidities. The advanced and targeted strategies against breast cancer have gained considerable attention due to their potential enhanced therapeutic efficacy over conventional therapies. In this context, phototherapies like photodynamic therapy (PDT) and photothermal therapy (PTT) have shown promise as an effective and alternative strategy due to reduced side effects, noninvasiveness, and spatiotemporal specificity. With the advent of nanotechnology, several types of nanomaterials that have shown excellent prospects in increasing the efficacy of photo therapies have been exploited in cancer treatment. In recent years, 2D nanomaterials have stood out promising because of their unique ultrathin planar structure, chemical, physical, tunable characteristics, and corresponding remarkable physiochemical/biological properties. In this review, the potential and the current status of several types of 2D nanomaterials such as graphene-based nanomaterials, Mxenes, Black phosphorous, and Transition Metal Dichalcogenides for photo/thermo and combination-based imaging and therapy of breast cancer have been discussed. The current challenges and prospects in terms of translational potential in future clinical oncology are highlighted., (© 2024 Wiley‐VCH GmbH.)

Surface-enhanced resonance Raman scattering (SERRS) in the second near-infrared (NIR-II) window has great potential for improved phototheranostics, but lacks nonfluorescent, resonant and high-affinity Raman dyes. Herein, it is designed and synthesize a multi-sulfur Raman reporter, NF1064, whose maximum absorption of 1064 nm rigidly resonates with NIR-II excitation laser while possessing absolutely nonfluorescent backgrounds. Ultrafast spectroscopy suggests that the fluorescence quenching mechanism of NF1064 originates from twisted intramolecular charge transfer (TICT) in the excited state. Gold nanorods (AuNRs) decorated with such nonfluorescent NF1064 (AuNR@NF1064) show remarkable SERRS performances, including zero-fluorescence background, femtomolar-level sensitivity as well as superb photostability without fluorescence photobleaching. More importantly, AuNR@NF1064 exhibits a nonlinear photothermal effect upon plasmonic fields of AuNRs by amplifying the non-radiative decay of nonfluorescent NF1064, thus achieving a high photothermal conversion of 68.5% in NIR-II window with potential for further augmentation. With remarkable SERRS and photothermal properties, the NIR-II nanoprobes allow for high-precision intraoperative guided tumor resection within 8 min, and high-efficient hyperthermia combating of drug-resistant bacterial infection within living mouse body. This work not only unlocks the potential of nonfluorescent resonant dyes for NIR-II Raman imaging, but also opens up a new method for boosting photothermal conversion efficiency of nanomaterials., (© 2024 Wiley‐VCH GmbH.)

Modern molecular imaging routes, such as nuclear imaging and optical imaging, derive significant advantages from nanoparticles, where multimodality use and multipurpose are key benefits. Nanoparticles also showcase benefits over traditional imaging agents in nuclear and optical imaging, including improved resolution, penetration, and specificity. The goal of this literature review was to explore recent advancements in nanomaterials within these molecular imaging techniques to expand on the current state of nanomedicine in these modalities. This review derives findings from relevant reviews, original research papers, in-human clinical trials, and patents in the literature. Au- and Fe oxide-based nanosystems are just as ubiquitous within more modern modalities due to their multimodal diagnostic and therapeutic potential. It is also repeatedly highlighted in the literature, patents, and clinical trials that the use of nanoparticles, specifically in multimodal imaging techniques and theranostics, present innovative methods in recent years, enabling researchers and clinicians to overcome the limitations of unimodal imaging modalities and further advancing accuracy in the diagnosis and treatment of important pathologies, particularly cancer. Overall, nanoparticle-based imaging represents a transformative approach in advanced imaging modalities, offering new approaches to limitations of conventional agents currently being applied in clinical settings.

Precise tumor diagnosis and treatment remain complex challenges. While numerous fluorescent probes have been developed for tumor-specific imaging and therapy, few exhibit effective function in vivo. Herein, a probe called TQ-H 2 is designed that can realize robust theranostic effects both in vitro and in vivo. In vitro, TQ-H 2 specifically targets the lysosome and reacts with hydroxyl radical (·OH) to generate TQ-HA, which lights up the cells. TQ-HA generates reactive oxygen species (ROS) under light irradiation, enabling the simultaneous induction and monitoring of apoptosis and ferroptosis in tumor cells. Remarkably, TQ-HA also acts as a self-amplifier, autocatalytically activating TQ-H 2 by generating ·OH under light exposure. This self-amplification aligns with the tumor microenvironment, where TQ-H 2 undergoes chemical transformation, distinguishing tumors from healthy tissue via near-infrared (NIR) fluorescence imaging. Furthermore, ROS generated by TQ-HA effectively kills tumor cells and inhibits tumor growth without harming normal cells. This study offers a promising strategy for targeted tumor theranostics using self-amplifying microenvironment-responsive fluorescent probes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Glioblastoma multiforme (GBM) is one of the most common and malignant brain tumors, with a high prevalence in elderly population. Most chemotherapeutic agents fail to reach the tumor site due to various challenges. However, smart nanocarriers have demonstrated excellent drug-loading capabilities, enabling them to cross the blood brain tumor barrier for the GBM treatment. Surface modification of nanocarriers has significantly enhanced their potential for targeting therapeutics. Moreover, recent innovations in drug therapies, such as the incorporation of theranostic agents in nanocarriers and antibody-drug conjugates, have offered newer insights for both diagnosis and treatment. This review focuses on recent advances in new therapeutic interventions for GBM, with an emphasis on the nanotheranostics systems to maximize therapeutic and diagnostic outcomes.

Rationale: Cancer remains a leading cause of mortality, with aggressive, treatment-resistant tumors posing significant challenges. Current combination therapies and imaging approaches often fail due to disparate pharmacokinetics and difficulties correlating drug delivery with therapeutic response. Methods: In this study, we developed radionuclide-activatable theranostic nanoparticles (NPs) comprising folate receptor-targeted bimetallic organo-nanoparticles (Gd-Ti-FA-TA NPs). Polyvalent tannic acid was used to coordinate titanium (Ti), a reactive oxygen species (ROS)-generating catalyst, gadolinium (Gd), a magnetic resonance imaging (MRI) contrast agent, and cypate, a near-infrared fluorescent dye. Results: The NPs exhibited higher magnetic field-dependent relaxivities ( r 1 = 20.8 mM⁻¹s⁻¹, r 2 = 72.1 mM⁻¹s⁻¹) than Gd-DTPA ( r 1 = 4.8 mM⁻¹s⁻¹, r 2 = 4.9 mM⁻¹s⁻¹) on a 3 T MRI scanner. Tannic acid coordination reduced the Ti band gap from 3.3 eV in TiO₂ NPs to 2.0 eV, tripling ROS generation under UV light exposure. In breast cancer models (4T1 and PyMT-Bo1), Cerenkov radiating radiopharmaceuticals activated Gd-Ti-FA-TA NPs in vitro and in vivo , generating cytotoxic ROS to inhibit tumor cell viability and prevent tumor progression. In vivo , the NPs selectively accumulated in 4T1 tumors and enhanced both T 1 and T 2 MRI contrast, highlighting a strategy to locally activate cytotoxic ROS generation with radiopharmaceuticals for cancer treatment, utilizing cross-modality PET/MRI and optical imaging for shallow and deep tissue visualization. Conclusion: The integrated nanoplatform allows direct imaging of drug delivery, providing guidance for the optimal timeline to activate therapeutic effects of pro-theranostic NPs via external triggers such as radionuclide-stimulated dynamic treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Theranostic drugs represent an emerging path to deliver on the promise of precision medicine. However, bottlenecks remain in characterizing theranostic targets, identifying theranostic lead compounds, and tailoring theranostic drugs. To overcome these bottlenecks, we present the Theranostic Genome, the part of the human genome whose expression can be utilized to combine therapeutic and diagnostic applications. Using a deep learning-based hybrid human-AI pipeline that cross-references PubMed, the Gene Expression Omnibus, DisGeNET, The Cancer Genome Atlas and the NIH Molecular Imaging and Contrast Agent Database, we bridge individual genes in human cancers with respective theranostic compounds. Cross-referencing the Theranostic Genome with RNAseq data from over 17'000 human tissues identifies theranostic targets and lead compounds for various human cancers, and allows tailoring targeted theranostics to relevant cancer subpopulations. We expect the Theranostic Genome to facilitate the development of new targeted theranostics to better diagnose, understand, treat, and monitor a variety of human cancers., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) remains a significant clinical challenge, urgently requiring effective intervention strategies. In recent years, the application of radiopharmaceuticals has emerged as a promising modality for the accurate diagnosis and treatment of malignancies. Due to its high expression on pancreatic cancer cells, mesothelin (MSLN) has become an appealing target for radioimmunotherapy (RIT). In this study, we report the development of a novel radiotracer by conjugating amatuximab with zirconium-89 ( 89 Zr) to facilitate the non-invasive detection of MSLN expression. Immuno-positron emission tomography (immunoPET) imaging demonstrated a specific accumulation of 89 Zr-DFO- amatuximab in PANC-1-MSLN tumors. Subsequently, Lutetium-177 ( 177 Lu)-labeled amatuximab was utilized for MSLN- targeted radioimmunotherapy (RIT), resulting in a significant suppression of PANC-1-MSLN xenograft growth. Furthermore, in vivo studies indicated that 177 Lu-DOTA-amatuximab exhibited limited side effects. The development of 89 Zr/ 177 Lu-labeled amatuximab may provide novel insights into the formulation of precision diagnostic and therapeutic strategies for MSLN- overexpressing tumors, including PDAC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prostate cancer ranks as the fourth most common cancer among men, with approximately 1.47 million new cases reported annually. The emergence of prostate-specific membrane antigen (PSMA) as a critical biomarker has revolutionized the diagnosis and treatment of prostate cancer. Recent advancements in low-molecular-weight PSMA inhibitors, with their diverse chemical structures and binding properties, have opened new avenues for research and therapeutic applications in prostate cancer management. These novel agents exhibit enhanced tumor targeting and specificity due to their small size, facilitating rapid uptake and localization at the target site while minimizing the retention in non-target tissues. The primary aim of this study is to evaluate the potential of low-molecular-weight PSMA inhibitors labeled with radioisotopes as theranostic agents for prostate cancer. This includes assessing their efficacy in targeted imaging and therapy and understanding their pharmacokinetic properties and mechanisms of action. This study is a literature review focusing on in vitro and clinical research data. The in vitro studies utilize PSMA-targeted radioligands labeled with radioisotopes to assess their binding affinity, specificity, and internalization in prostate cancer cell lines. Additionally, the clinical studies evaluate the safety, effectiveness, and biodistribution of radiolabeled PSMA ligands in patients with advanced prostate cancer. The findings indicate promising outcomes regarding the safety and efficacy of PSMA-targeted radiopharmaceuticals in clinical settings. The specific accumulation of these agents in prostate tumor lesions suggests their potential for various applications, including imaging and therapy. This research underscores the promise of radiopharmaceuticals targeting PSMA in advancing the diagnosis and treatment of prostate cancer. These agents improve diagnostic accuracy and patients' outcomes by enhancing imaging capabilities and enabling personalized treatment strategies.

Nanoparticle-based therapies represent a transformative approach to managing gynecological cancers, offering targeted treatment strategies that minimize harm to healthy tissues while maximizing therapeutic efficacy. Despite their potential, implementing these advanced treatments in Africa is needed by a complex interplay of technological, economic, regulatory, and ethical challenges. This paper examines the current landscape of nanoparticle-based therapies, identifying critical barriers to their adoption, including inadequate infrastructure, high costs, and insufficient regulatory frameworks. Technological deficiencies manifest as a need for advanced nanoparticle synthesis, delivery, and diagnostics equipment, impeding research and clinical applications. Economically, the high production costs of nanoparticles, compounded by limited access to advanced diagnostic and treatment facilities, create significant financial barriers for healthcare systems and patients alike. Additionally, the regulatory environment needs to be more cohesive, characterized by a lack of established protocols and expertise to evaluate the unique properties of nanomedicines. However, opportunities for advancement exist through focused research and development initiatives. Targeted drug delivery systems, early detection methods, and immunotherapy integration are promising avenues to enhance treatment outcomes. Collaborative partnerships between African institutions and international research entities, alongside public-private collaborations, could bolster local capabilities in nanomedicine. To facilitate the integration of nanoparticle-based therapies, African governments must prioritize funding for nanomedicine research, create robust regulatory frameworks, and ensure equitable access to these innovative treatments. A concerted effort involving policy reforms, investment, and collaboration is essential for overcoming existing barriers and realizing the full potential of nanoparticle-based therapies in improving health outcomes for gynecological cancer patients across Africa., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The study was approved by the ethics committee of the selected universities. Informed consent was obtained from all participating students, ensuring that their participation was voluntary and that their confidentiality was maintained throughout the study. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The rapid development of nanotechnology during the last two decades has created new opportunities to design and generate more advanced nanotheranostics with diversified capabilities for diagnosis, drug delivery, and treatment response monitoring in a single platform. To date, several approaches have been employed in order to develop nanotheranostics. The purpose of this review is to briefly discuss the key components of nanotheranostic systems, to present the conventional and upcoming imaging and therapeutic modalities that employ nanotheranostic systems, and to evaluate recent progress in the field of cancer nanotheranostic systems in the past five years (2020-2024). Special attention is focused on the design of cancer nanotheranostic systems, their composition, specificity, potential for multimodal imaging and therapy, and in vitro and in vivo characterization.

The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity and retention but affects biodistribution and pharmacokinetics. Amide formation of the terminal carboxylic acid moieties of the square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives with 4, 3, and 2 terminal azides and zero, 1, and 2 remaining carboxylic acids, respectively, whereby formation of the 2-cis-isomer is preferred according to NMR investigation of the Eu(III)-complexes. Cu(II)-catalyzed alkyne-azide cycloaddition (CuAAC) of the alkyne-functionalized αvβ6-integrin binding peptide cyclo[YRGDLAYp( N Me)K(pent-4-ynoic amide)] (Tyr2) yields the respective di-, tri-, and tetrameric conjugates for Lu-177-labeling. In mice bearing αvβ6-integrin-expressing xenografts of H2009 (human lung adenocarcinoma) cells, the Lu-177-labeled trimer's tumor-to-blood ratio of 112 exceeds that of the tetramer (10.4) and the dimer (54). Co-infusion of gelofusine (succinylated gelatin) reduces the renal uptake of the trimer by 89%, resulting in a 10-fold better tumor-to-kidney ratio, while no improvement of that ratio is observed with arginine/lysine, para -aminohippuric acid (PAH), and hydroxyethyl starch (HES) coinfusions. Since the Lu-177-labeled Tyr2-trimer outperforms the dimer and the tetramer, such trimers are considered the best lead structures for the ongoing development of αvβ6-integrin targeted anticancer theranostics.

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores. First-in-human 64 Cu-FBP8 fibrin-targeted positron emission tomography (PET) imaging in seven patients with gastric or gastroesophageal junction cancer showed high probe uptake in all target lesions with tumor-to-background (muscle) uptake ratios of 9.9 ± 6.6 in primary ( n = 7) and 11.2 ± 6.6 in metastatic ( n = 45) tumors. Using two mouse models of human GCa, one fibrin-high (SNU-16) and one fibrin-low (NCI-N87), we showed that PET imaging with a related fibrin-specific peptide, CM500, labeled with copper-64 ( 64 Cu-CM500) specifically bound to and precisely quantified tumor fibrin in both models. We then labeled the fibrin-specific peptide CM600 with yttrium-90 and showed that 90 Y-CM600 effectively decreased tumor growth in these mouse models. Mice carrying fibrin-high SNU-16 tumors experienced tumor growth inhibition and prolonged survival in response to either a single high dosage or fractionated lower dosage of 90 Y-CM600, whereas mice carrying fibrin-low NCI-N87 tumors experienced prolonged survival in response to a fractionated lower dosage of 90 Y-CM600. These results lay the foundation for a fibrin-targeted theranostic that may expand options for patients with advanced GCa.

Purpose: Effective cancer treatment relies on the precise deployment of clinical imaging techniques to accurately treat tumors. One highly representative technology among these is multi-imaging guided phototherapy. This work introduces a new and innovative theranostic drug that combines near-infrared (NIR) irradiation-induced photodynamic therapy (PDT) and photothermal therapy (PTT) to treat malignancies. Moreover, it can be utilized as a contrasting substance for X-ray computed tomography (CT) imaging and contrast-enhanced ultrasound (CEUS) to aid in the administration of therapy., Methods: Cesium tungsten bronze nanobubbles (Cs x WO 3 @NBs) were constructed via a water-controlled solvothermal synthesis and thin film hydration of phospholipid. Various methods, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy, were used to analyze and describe the size, shape, and chemical characteristics of the nanoparticles. In this study, hepatoma cell lines HepG2 and HUH7 were employed in vitro, and xenotransplantation mouse models were used to assess their antitumor effects. A series of in vitro and in vivo trials were conducted to assess the effectiveness of combining photodynamic and photothermal therapies, as well as using CEUS and CT imaging., Results: The Cs x WO 3 @NBs exhibit photothermal effects and the generation of reactive oxygen species (ROS) under laser irradiation, thereby enabling effective photothermal and photodynamic combinatorial therapy. Following combined treatment, the activity and invasive capacity of hepatocellular carcinoma cells were markedly diminished, the development rate of the tumor was noticeably reduced, and the level of biological toxicity was low. Additionally, Cs x WO 3 @NBs possess the capacity to serve as both a CT imaging agent and a contrast-enhanced ultrasound agent., Conclusion: Cs x WO 3 @NBs represent a promising theranostic agent for image-guided cancer therapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

This review aims to address the significant challenges of treating central nervous system (CNS) disorders such as neurodegenerative diseases, strokes, spinal cord injuries, and brain tumors. These disorders are difficult to manage due to the complexity of disease mechanisms and the protective blood-brain barrier (BBB), which restricts drug delivery. Recent advancements in nanoparticle (NP) technologies offer promising solutions, with potential applications in drug delivery, neuroprotection, and neuroregeneration. By examining current research, we explore how NPs can cross the BBB, deliver medications directly to targeted CNS regions, and enhance both diagnostics and treatment. Key NP strategies, such as passive targeting, receptor-mediated transport, and stimuli-responsive systems, demonstrate encouraging results. Studies show that NPs may improve drug delivery, minimize side effects, and increase therapeutic effectiveness in models of Alzheimer's, Parkinson's, stroke, and glioblastoma. NP technologies thus represent a promising approach for CNS disorder management, combining drug delivery and diagnostic capabilities to enable more precise and effective treatments that could significantly benefit patient outcomes.

Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology. These include the need for molecular imaging or surgical window-of-opportunity studies to confirm adequate passage across the blood-brain barrier, optimize eligibility criteria, and selection of the most appropriate response criteria and endpoints to address issues such as pseudoprogression. This review will discuss some of the issues that should be considered when designing clinical trials for theranostic agents., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Radiopharmaceutical theranostic treatments have grown exponentially worldwide, and internal dosimetry has attracted attention and resources. Despite some similarities with chemotherapy, radiopharmaceutical treatments are essentially radiotherapy treatments, as the release of radiation into tissues is the determinant of the observed clinical effects. Therefore, absorbed dose calculations are key to explaining dose-effect correlations and individualizing radiopharmaceutical treatments. The present article introduces the basic principles of internal dosimetry and provides an overview of available loco-regional and systemic radiopharmaceutical treatments for central nervous system (CNS) tumors. The specific characteristics of dosimetry as applied to these treatments are highlighted, along with their limitations and most relevant results. Dosimetry is performed with higher precision and better reproducibility than in the past, and dosimetric data should be systematically collected, as treatment planning and verification may help exploit the full potential of theranostic of CNS tumors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Achieving accurate and efficient tumor imaging is crucial in the field of tumor treatment, as it facilitates early detection and precise localization of tumor tissues, thereby informing therapeutic strategies and surgical interventions. The optical imaging technology within the second near-infrared (NIR-II) window has garnered significant interest for its remarkable benefits, such as enhanced tissue penetration depth, superior signal-to-background ratio (SBR), minimal tissue autofluorescence, reduced photon attenuation, and lower tissue scattering. This review explained the design and optimization strategies of nano-agents responsive to the NIR-II window, such as single-walled carbon nanotubes, quantum dots, lanthanum-based nanomaterials, and noble metal nanomaterials. These nano-agents enable non-invasive, deep-tissue imaging with high spatial resolution in the NIR-II window, and their superior optical properties significantly improve the accuracy, efficiency, and versatility of imaging-guided tumor treatments. And we discussed the characteristics and advantages of fluorescence imaging (FL)/photoacoustic imaging (PA) in NIR-II window, providing a comprehensive overview of the latest research progress of different nano-agents in FL/PA imaging-guided tumor therapy. Furthermore, we exhaustively reviewed the latest applications of multifunctional nano-phototherapy technologies carried out by NIR-II light including photothermal therapy (PTT), photodynamic therapy (PDT), and combined modalities like photothermal-chemodynamic therapy (PTT-CDT), photothermal-chemotherapy (PTT-CT), and photothermal- immunotherapy (PTT-IO). These imaging-guided integrated tumor therapy approaches within the NIR-II window have gradually matured over the past decade and are expected to become a safe and effective non-invasive tumor treatment. Finally, we outlined the prospects and challenges of development and innovation of the NIR-II integrated diagnosis and therapy nanoplatform. This review aims to provide insightful perspectives for future advancements in NIR-II optical tumor diagnosis and integrated treatment platforms.

The commonly employed strategies for engineering second near-infrared (NIR-II) organic phototheranostic agents are based on expanding conjugated backbone length, strengthening donor (D)-acceptor (A) effect, or forming J-aggregates. We constructed the D-A-D' structure by incorporating strong electron-donating methoxy and tetraphenylethene (TPE) moieties on the electron-deficient Aza-BODIPY core, and simultaneously expanded the π-conjugation effect by introducing thiophene groups, to obtain a dye BDP-TPE. Next, the nanoparticles P-TPE were prepared via the assembly of BDP-TPE with amphiphilic polypeptides (mPEG 2000 -P(Asp) 10 ), and successfully constructed the J-aggregates. The obtained P-TPE exhibited strong absorption and fluorescence with maxima at 808 and 1018 nm, respectively, with a conspicuous absolute quantum yield of 0.241 %. Moreover, P-TPE also showed excellent biocompatibility, and high photothermal conversion efficiency of 61.15 %, and excellent resistance to pH, long-term storage, and photobleaching. In vitro and in vivo experiments revealed that P-TPE exhibited good biocompatibility and effectively achieved NIR-II fluorescence imaging-guided PTT with complete tumor ablation under 808 nm laser irradiation. These results provided good evidence for the use of P-TPE as a NIR-II fluorescence imaging-guided PTT therapeutic agent in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

It is widely acknowledged that gold-based materials are of significant interest in the field of biomedicine. Consequently, considerable efforts have been devoted to identifying gold nanoparticles that exhibit effective performance in tumor diagnosis and treatment. However, the underlying reasons for the enhanced efficacy of these gold-based nanomaterials in cancer therapy and diagnosis remain unclear, primarily due to the lack of an in-depth understanding of the mechanisms involved. Therefore, it is essential to summarize the progress in the field to facilitate the rational design of more efficient nanodevices. In this review, we present recent achievements drawn from the latest research to demonstrate the broad applications of gold-based materials. We begin by illustrating the mechanisms of gold-derived nanoparticles during therapeutic and diagnostic processes, including photothermal therapy, photodynamic therapy, sonodynamic therapy, photoacoustic tomography, fluorescence imaging, and X-ray computed tomography. We then summarize the advancements of gold-based nanomaterials in cancer diagnosis and treatment while also analyzing the factors contributing to their enhanced performance. Finally, we highlight key descriptors for evaluating the efficacy and strategies for designing high-performance nanomaterials. This review aims to pave the way for addressing future challenges and outlines directions for the advancement of gold-based biomedicine.

Introduction: Breast cancer is one of the main causes of mortality in women globally. Early and accurate diagnosis represents a milestone in cancer management. Several breast cancer diagnostic agents are available. Many chemotherapeutic agents in conventional dosage forms are approved; nevertheless, they lack cancer cell specificity, resulting in improper treatment and undesirable side effects. Recently, nanotheranostics has emerged as a new paradigm to achieve safe and effective cancer diagnosis and management., Area Covered: This review provides insight into breast cancer epidemiology, barriers hindering the early diagnosis, and effective delivery of chemotherapeutics. Also, conventional diagnostic agents and recent nanotheranostic platforms have been used in breast cancer. In addition, mechanisms of cancer cell targeting and nano-carrier surface functionalization as an effective approach for chemotherapeutic targeting were reviewed along with future perspectives., Expert Opinion: We proposed that modified nano-carriers may provide an efficacious approach for breast cancer drug targeting. These nanotheranostics need more clinical evaluations to confirm their efficacy in cancer management. In addition, we recommend the use of artificial intelligence (AI) as a promising approach for early and efficient assessment of breast lesions. AI allows better interpretation and analysis of nanotheranostic data, which minimizes misdiagnosis and avoids the belated intervention of health care providers.

Immune checkpoint inhibitors (ICIs) are innovative immunotherapeutic agents for cancer. However, their low therapeutic efficacy in patients with large or rapidly growing tumors, along with their high cost, represents a notable limitation in their clinical applications. Therefore, new and safe strategies must be developed to enhance the therapeutic efficacy of ICIs in clinical settings. In this study, we developed a near-infrared (NIR) fluorescent dye-loaded activatable theranostic nanogel (NATNgel) for precision imaging-guided photodynamic therapy (PDT) and combined immunotherapy for rapidly growing tumors. Although NIR fluorescence and phototoxicity of NATNgel are strongly quenched, these can be selectively activated inside target tumor cells. A high tumor-to-background ratio (7.31 ± 1.40) in NIR fluorescence imaging could be achieved in NATNgel-treated mice, enabling real-time image-guided PDT. The combination of PDT and anti-PD-1 antibody therapy resulted in complete tumor regression. Histopathological evaluation of major organs and blood chemistry analysis revealed no side effects of the combined treatment regimen. In addition, the combination treatment completely suppressed the growth of rechallenged tumors. Overall, NATNgel is a safe and promising theranostic material for precision imaging-guided PDT and enhanced immunotherapy., Competing Interests: Declaration of competing interest The authors declare no conlict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abnormally elevated levels of reactive oxygen species (ROS) are considered one of the characteristics of tumors and have been extensively employed in the construction of tumor-activated prodrugs. However, ideal ROS-activated molecular triggers that possess high sensitivity and easy functionalization for tailoring specific prodrugs, remain scarce. In this work, we developed a highly reactive oxygen species (hROS, such as •OH, ONOO - and HOCl)-responsive molecular trigger (namely FDROS-4) through the conjunction of methylene blue (MB) and 2, 6-bis (hydroxymethyl) aniline via urea bond, integrating imaging and therapeutic functions. FDROS-4 could be readily modified as multifunctional prodrugs and efficiently activated by hROS, leading to the release of near-infrared emissive MB and parent drugs. By using chlorambucil as a model drug and incorporating varying numbers of galactose as liver-targeting ligands, we designed and synthesized a series of prodrugs named FDROS-6, FDROS-7, and FDROS-8. The optimal prodrug, FDROS-7, could self-assemble into monocomponent nanoparticles, exhibiting enhanced biocompatibility and therapeutic efficacy compared to the parent drug. This hROS-activated molecular trigger holds promise for the development of stimulus-responsive prodrugs in chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cancer immunotherapy remains a low immune response rate in clinic because of dominant immunosuppressive tumor microenvironment (TME) and lack of effective drug to specifically remodel the TME. In this work, we introduced a tumor-seeking human serum albumin (HSA) based delivery platform by covalently conjugating with a tumor-targeting near-infrared (NIR) photosensitizer (IR-DBI) and non-covalently loading of immune modulator Resiquimod (R848). HSA exhibited tumor-preferential accumulation after covalent conjugation with IR-DBI. Meanwhile, HSA restricted the rotation of IR-DBI, narrowed the HOMO-LUMO energy gap, significantly enhanced fluorescent intensity and dual-modal phototherapy (PTT/PDT). The enhanced phototherapeutic effect further induced robust ICD effect. More importantly, non-covalent loading of R848 could be released from HSA at tumor sites by laser irradiation-induced heat. The in-situ release of R848 in TME efficiently promoted the maturation of DC cells and repolarized M2 macrophages to M1 macrophages. Consequently, robust photo-induced antitumor immunity was triggered in the different mice models bearing primary and distant tumors or lung metastasis, which was further enhanced by combining with CTLA-4 blockade therapy. Taken together, this work may present a versatile albumin composite which exhibits tumor-preferential accumulation and imaging-guided PDT/PTT/immunotherapy., Competing Interests: Declaration of Competing Interest We certify that our work reported in this paper is an original work and has not been published previously, including in any form of a preprint, an abstract, a published lecture, academic thesis or registered report. The article's publication is approved by all authors and explicitly by the responsible authorities where the work was carried out. If accepted, the article will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dendrimers and supramolecular chemistry continue to fascinate researchers due to the endless unrevealed potential of their combination. This study investigates the self-assembly process of a series of hydrophobic triazolylferrocenyl dendrimers in aqueous medium. Deep investigation through NMR spectroscopy, absorption UV-vis spectroscopy along with theoretical simulations demonstrates that the ferrocenyl moieties interact intramolecularly and intermolecularly driving the self-assembly process. Data obtained by DLS, NTA, SEM, TEM, and EF-TEM demonstrate that these dendrimers, in water, spontaneously self-assemble through a hierarchical process. The dendrimers first self-assemble into uniform nanovesicles, which in turn self-assemble into larger vesosomes. The resulting vesosomes emit green non-traditional intrinsic fluorescence, which is a property that emerged from the self-assembled architectures. The vesosomes are efficiently uptaken by cancer cells and induce significant cytotoxic activity against the cancer cell line MCF-7, up to the submicromolar concentration. Positive dendritic effects are identified in the fluorescence intensity and in the cytotoxic activity of the vesosomes, which follow the trend G0-9Fc < G1-27Fc < G2-81Fc. This work showcases the remarkable potential of combining the two dynamic fields of dendrimers and supramolecular chemistry, which resulted in green fluorescent vesosomes capable of performing the dual role of cell imaging and killing, with potential applications in nanotheranostics., (© 2024 Wiley‐VCH GmbH.)