Search

Endometriosis, the growth of endometrial-like tissue outside the uterus, causes chronic pain and infertility in 10 % of reproductive-aged women worldwide. Unfortunately, no permanent cure exists, and current medical and surgical treatments offer only temporary relief. Endometriosis is a chronic inflammatory disease characterized by immune system dysfunction. Our previous study showed aberrant activation of signal transducer and activator of transcription 3 (STAT3) in endometriosis. Our transcriptomic analysis of uterine tissue from uterine-specific Stat3 knock-out mice identifies that STAT3 regulates inflammatory and immune-related genes. Here, we evaluate cerium-oxide nanoparticles (nanoceria) as a non-steroidal anti-inflammatory drug for endometriosis theranostics. Our in vitro studies validate the multi-enzymatic properties of nanoceria, enabling the transition of pro-inflammatory macrophages to an anti-inflammatory state in J774 macrophage cells. In vivo, treatment of endometriosis mice with nanoceria reveals its ability to passively accumulate at ectopic lesions. The nanoceria conjugated with indocyanine green are non-invasively trackable to ectopic lesions. Therefore, immune modulation and anti-inflammatory effects of nanoceria significantly reduce development of ectopic lesions while minimizing off-target effects, such as avoiding interference with pregnancy including implantation and decidualization. Our results suggest that aberrant STAT3 activation is a major contributor to endometriosis, and nanoceria offers a novel theranostic approach for endometriosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biomacromolecules play a critical role in advancing disease diagnosis and treatment. Traditional carriers often lack real-time tracking capabilities, controlled drug release, and may induce adverse effects for delivering biomacromolecules. Aggregation-induced emission luminogens (AIEgens) provide significant advantages in biomacromolecule delivery, enabling real-time fluorescence imaging and reactive oxygen species generation for photodynamic therapy (PDT). This dual functionality allows for the visualization of the biomacromolecule delivery process, providing valuable insights into biodistribution, cellular uptake, and drug-cell interactions. Additionally, the light-responsive nature of AIEgens enables precise spatial-temporal control over cargo release and imaging-guided PDT with minimal side effects. In this perspective, we summarize recent advancements in the use of AIEgens for visualized delivery and light-controlled theranostic applications of biomacromolecules, highlighting their potential to overcome challenges in targeted imaging and precision treatments. Key topics covered include covalent linkage strategies and the biomedical applications of AIEgen-functionalized biomacromolecules, including nucleic acids, proteins, polysaccharides, and lipids. We further highlight AIEgen-functionalized gene therapy and PDT for cancer, peptide transport for disease diagnosis, as well as polysaccharides and lipids delivery in antimicrobial treatments. This perspective concludes by addressing future challenges and opportunities, emphasizing the potential of AIEgen-functionalized biomacromolecules to advance precision theranostics., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

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.)

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.)

Although smart contact lenses have demonstrated great potential in theranostics, there remain critical challenges and opportunities in their commercial development. In this Perspective, the current status and capability of smart theranostic contact lenses are highlighted, focusing on their application as sensing systems for detecting biomarkers such as glucose, intraocular pressure (IOP), and inflammatory cytokines, and as drug delivery systems (DDS) for precise and controlled therapy. Additionally, key challenges associated with clinical development and commercialization of smart theranostic contact lenses are discussed, to optimize diagnostic and therapeutic interventions. Considering the rapid evolution of the field, we finally also discuss the need for systematic studies on safety, efficacy, and mass-production, and we spark new ideas for advancing smart theranostic contact lenses into versatile platforms for personalized medicine., Competing Interests: Declaration of competing interest None., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Recently, micro/nanorobots (MNRs) with self-propulsion have emerged as a promising smart platform for diagnostic, therapeutic and theranostic applications. Especially, polymer-based MNRs have attracted huge attention due to their inherent biocompatibility and versatility, making them actively explored for various medical applications. As the translation of MNRs from laboratory to clinical settings is imperative, the use of appropriate polymers for MNRs is a key strategy, which can prompt the advancement of MNRs to the next phase. In this review, we describe the multifunctional versatile polymers in MNRs, and their biodegradability, motion control, cargo loading and release, adhesion, and other characteristics. After that, we review the theranostic applications of polymer-based MNRs to bioimaging, biosensing, drug delivery, and tissue engineering. Furthermore, we address the challenges that must be overcome to facilitate the translational development of polymeric MNRs with future perspectives. This review would provide valuable insights into the state-of-the-art technologies associated with polymeric MNRs and contribute to their progression for further clinical development., 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.)

Corneal neovascularization (CNV) is a major cause of blindness worldwide. However, the recent drug treatment is limited by repeated administration and low drug bioavailability. In this work, SU6668 (an inhibitor of receptor tyrosine kinases) and indocyanine green (ICG) are loaded onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and then coated with anti-VEGFR2 single chain antibody (AbVr2 scFv) genetically engineered cell membrane vesicles. The nanomedicine is delivered via eye drops, and the hyperthermia induced by laser irradiation could block the blood vessels. Meanwhile, the photothermal effect can also cause the degradation of nanomaterials and release chemotherapeutic drugs in the blocked area, thereby continuously inhibit the neovascularization. Furthermore, SU6668 could inhibit the expression of heat shock protein 70 (HSP70), promoting the cell death induced by photothermal effect. In conclusion, the combination of photothermal and chemotherapy drugs provides a novel, effective and safe approach for the treatment of CNV., 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.)

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T 1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Protein-based nanoparticles have garnered significant attention in theranostic applications due to their superior biocompatibility, exceptional biodegradability and ease of functionality. Compared to other nanocarriers, protein-based nanoparticles offer additional advantages, including biofunctionality and precise molecular recognition abilities, which make them highly effective in navigating complex biological environments. Moreover, proteins can serve as powerful tools with self-assembling structures and reagents that enhance cell penetration. And their derivation from abundant renewable sources and ability to degrade into harmless amino acids further enhance their suitability for biomedical applications. However, protein-based nanoparticles have so far not realized their full potential. In this review, we summarize recent advances in the use of protein nanoparticles in tumor diagnosis and treatment and outline typical methods for preparing protein nanoparticles. The review of protein nanoparticles may provide useful new insights into the development of biomaterial fabrication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glycosylated nanoplatforms have emerged as promising tools in the field of cancer theranostics, integrating both therapeutic and diagnostic functionalities. These nanoscale platforms are composed of different materials such as lipids, polymers, carbons, and metals that can be modified with glycosyl moieties to enhance their targeting capabilities towards cancer cells. This review provides an overview of different modification strategies employed to introduce glycosylation onto nanoplatforms, including chemical conjugation, enzymatic methods, and bio-orthogonal reactions. Furthermore, the potential applications of glycosylated nanoplatforms in cancer theranostics are discussed, focusing on their roles in drug delivery, imaging, and combination therapy. The ability of these nanoplatforms to selectively target cancer cells through specific interactions with overexpressed glycan receptors is highlighted, emphasizing their potential for enhancing efficacy and reducing the side effects compared to conventional therapies. In addition, the incorporation of diagnostic components onto the glycosylated nanoplatforms provided the capability of simultaneous imaging and therapy and facilitated the real-time monitoring of treatment response. Finally, challenges and future perspectives in the development and translation of glycosylated nanoplatforms for clinical applications are addressed, including scalability, biocompatibility, and regulatory considerations. Overall, this review underscores the significant progress made in the field of glycosylated nanoplatforms and their potential to revolutionize cancer 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 B.V. All rights reserved.)

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an effective way to initiate an immune response against tumors, and the research on agonists targeting STING has become a new hotspot in the development of antitumor drugs. However, as a novel STING agonist, the limited bioavailability and activation routes of manganese ions (Mn 2+ ) significantly hinder its antitumor effects. To address these challenges, we have designed a metal-coordinated nucleoside metabolic inhibitor (gemcitabine, Gem)-induced metal nanotheranostic (MGP) with PEGylation. This formulation synergistically enhanced the immune response against cancer cells by sensitizing the cGAS-STING pathway and promoting immunogenic cell death (ICD). Modified with PEG derivatives, MGP was efficiently delivered to the tumor site and was internalized by cancer cells. Upon internalization, the release of Mn 2+ triggered the activation of the cGAS-STING pathway, while the release of Gem induced DNA damage. On the one hand, the damaged DNA caused by Gem leaked into the cytoplasm, synergistically amplified Mn 2+ -induced activation of the cGAS-STING pathway, and induced the production of the tumor cytotoxic factor IFN-β. On the other hand, Mn 2+ -mediated chemodynamic therapy (CDT) exhibited an ICD effect, which further synergized with the activation of the cGAS-STING pathway to promote dendritic cells (DCs) maturation and antigen-specific T cells infiltration. Both in vitro and in vivo studies have demonstrated that MGP nanotheranostics could elicit a robust antitumor effect, especially when combined with anti-PD-1. This study provided a new paradigm for intensifying immune activation by constructing metal coordination nanotheranostics., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Nanoparticle formulations blending optical imaging contrast agents and therapeutics have been a cornerstone of preclinical theranostic applications. However, nanoparticle-based theranostics clinical translation faces challenges on reproducibility, brightness, photostability, biocompatibility, and selective tumor targeting and penetration. In this study, we integrate multimodal imaging and therapeutics within cancer cell-derived nanovesicles, leading to biomimetic bright optotheranostics for monitoring cancer metastasis. Upon NIR light irradiation, the engineered optotheranostics enables deep visualization and precise localization of metastatic lung, liver, and solid breast tumors along with solid tumor ablation. Metastatic cell-derived nanovesicles (∼80 ± 5 nm) are engineered to encapsulate imaging (emissive organic dye and gold nanoparticles) and therapeutic agents (anticancer drug doxorubicin and photothermally active organic indocyanine green dye). Systemic administration of biomimetic bright optotheranostic nanoparticles shows escape from mononuclear phagocytic clearance with (i) rapid tumor accumulation (3 h) and retention (up to 168 h), (ii) real-time monitoring of metastatic lung, liver, and solid breast tumors and (iii) 3-fold image-guided solid tumor reduction. These findings are supported by an improvement of X-ray, fluorescence, and photoacoustic signals while demonstrating a tumor reduction (201 mm 3 ) in comparison with single therapies that includes chemotherapy (134 mm 3 ), photodynamic therapy (72 mm 3 ), and photothermal therapy (88mm 3 ). The proposed innovative platform opens new avenues to improve cancer diagnosis and treatment outcomes by allowing the monitorization of cancer metastasis, allowing the precise cancer imaging, and delivering synergistic therapeutic agents at the solid tumor site., Competing Interests: Declaration of competing interest J.C. is a co-founder and shareholder of TargTex S.A – Targeted Therapeutics for Glioblastoma Multiforme. J.C. is a member of the Global Burden Disease (GBD) consortium from Institute for Health Metrics and Evaluation (IHME), University of Washington (US). All the other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS)-sensitive theranostics hold great promise for personalized treatment of various diseases. However, most current theranostics rely on luminescence techniques with complex probe design, high background signals and bulky instruments. Herein, we propose a novel thermal signal-based theranostic for ROS monitoring by detecting the photothermal signal change of near-infrared (NIR)-active dye (IR820) that released from the porous silicon (PSi)-based carrier and demonstrate its application for synergistic theranostics of chronic wounds. Owing to the reduced energy level caused by J-aggregate formation and the improved non-radiative decay pathway, trapping of IR820 in calcium ion sealed PSi (I-CaPSi) exhibits significantly enhanced photothermal capability compared to free IR820. With the degradation of PSi induced by ROS, the trapped and aggregated IR820 is released to be dispersed and free state. Therefore, the decrease of photothermal signal in response to ROS stimuli can be recorded in real time. Using a portable smartphone equipped with a thermal camera, ROS levels at wounds can be monitored non-invasively and conveniently to indicate exacerbation or healing conditions. Moreover, the NIR-triggered smart delivery platform also triggers photothermal and photodynamic therapy to inhibit bacterial growth and exhibits bioactivity to promote cell migration and angiogenesis via the Si ions released from PSi. With the synergistic advantages of ROS-responsive property, pro-healing ability, anti-infection effect and excellent biosafety, the NIR-activated theranostic platform achieves convenient diagnosis and effective treatment in diabetic wound infection models in vivo. Overall, this work demonstrates a promising paradigm of I-CaPSi smart delivery platform with great clinical translation potential for home-based chronic wound theranostics., Competing Interests: Declaration of Competing Interest The author declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Ultrasound (US) is a mechanical wave that can penetrate biological tissues and trigger complex bioeffects. The mechanisms of US in different diagnosis and treatment are different, and the functional application of commercial US is also expanding. In particular, recent developments in nanotechnology have led to a wider use of US in precision medicine. In this review, we focus on US in combination with versatile micro and nanoparticles (NPs)/nanovesicles for tumor theranostics. We first introduce US-assisted drug delivery as a stimulus-responsive approach that spatiotemporally regulates the deposit of nanomedicines in target tissues. Multiple functionalized NPs and their US-regulated drug-release curves are analyzed in detail. Moreover, as a typical representative of US therapy, sonodynamic antitumor strategy is attracting researchers' attention. The collaborative efficiency and mechanisms of US and various nano-sensitizers such as nano-porphyrins and organic/inorganic nanosized sensitizers are outlined in this paper. A series of physicochemical processes during ultrasonic cavitation and NPs activation are also discussed. Finally, the new applications of US and diagnostic NPs in tumor-monitoring and image-guided combined therapy are summarized. Diagnostic NPs contain substances with imaging properties that enhance US contrast and photoacoustic imaging. The development of such high-resolution, low-background US-based imaging methods has contributed to modern precision medicine. It is expected that the integration of non-invasive US and nanotechnology will lead to significant breakthroughs in future clinical applications., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest regarding this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Photoacoustic imaging (PAI) of biological tissue has been a fast developing biomedical multi-wave imaging modality, after its introduction in the mid90s. PAI couples laser excitation to acoustic detection. Especially, in recent years its significant advantages in onco-surgery has attracted much attention due to its ability to detect malignant tissues. Monitoring cancer angiogenesis, assessment of blood oxygen saturation, functional brain imaging, evaluation of cortical blood volume, detection of skin/conjunctival melanoma depth, assessment of met-hemoglobin, investigating tumor hypoxia andcancer lymph node metastases are some of its promising applications. Moreover, as a real-time monitoring strategy, PAI allows intraoperative imaging of micro-metastases and residual islands in onco-surgery. Herein, we provide a brief introduction to biophysics and fundamentals of PAI, potential novel endogenous and exogenous contrast agents, and novel techniques to develop engineered and targeted contrast agents with theranostic applications. We also summarize the clinical trial pipelines for PAI. Furthermore, we discuss the potential obstacles and limitation of PAI theranostic agents for further clinical applications and strategies to overcome these hurdles., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To overcome drug resistance and improve precision theranostics for hepatocellular carcinoma (HCC), a nanoplatform with an "off/on" function for multimodality imaging (near-infrared-II (NIR-II) fluorescence imaging, magnetic resonance imaging (MRI), and photoacoustic imaging) and synergistic therapy (photodynamic therapy and ferroptosis) activated by an acidic pH in the tumor microenvironment is proposed. Although many photosensitizers with photodynamic effects have been reported, very few of them have outstanding photodynamic effect and high stability with response to endogenous stimuli capable of NIR-II imaging. Herein, a new amphiphilic photosensitizer SR780 derived from croconaine dye, was developed with satisfactory photodynamic effects and pH-responsive NIR-II imaging. Interestingly, it was deactivated by coordination with Fe 3+ (SR780@Fe) and activated during their release under mild acidic condition. Ferroptosis can generate hydroxyl free radical and lipid peroxide, which aggravate the oxidative stress of tumor cells and mediate their death while depleting glutathione (GSH) to enhance photodynamic effect. In situ pH-activatable theranostic nanoplatform, SR780@Fe-PAE-GP, was thus developed by loading SR780@Fe with pH-responsive polymers, modified by a glypican-3 (GPC-3) receptor-targeting peptide. The synergistic antitumor effects were confirmed both in vitro and in vivo, and the tumor inhibition rate of the SR780@Fe-PAE-GP + L treatment group reached 98%., Competing Interests: Declaration of Competing Interest All authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

World Health Organisation (WHO) delineated cancer as one of the foremost reasons for mortality with 10 million deaths in the year 2020. Early diagnosis and effective drug delivery are of utmost importance in cancer management. The entrapment of both bio-imaging dyes and drugs will open novel avenues in the area of tumor theranostics. Elevated levels of reactive oxygen species (ROS) and glutathione (GSH) are the characteristic features of the tumor microenvironment (TME). Researchers have taken advantage of these specific TME features in recent years to develop micelle-based theranostic nanosystems. This review focuses on the advantages of redox-sensitive micelles (RSMs) and supramolecular self-assemblies for tumor theranostics. Key chemical linkers employed for the tumor-specific release of the cargo have been discussed. In vitro characterisation techniques used for the characterization of RSMs have been deliberated. Potential bottlenecks that may present themselves in the bench-to-bedside translation of this technology and the regulatory considerations have been deliberated., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP (n = 1-4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Tumor-associated macrophages (TAMs), the main components of infiltrating leukocytes in tumors, often play a key role in promoting cancer development and progression. The tumor-specific microenvironment forces the phenotype of tumor-infiltrating to evolve in a direction favorable to tumor development, that is, the generation of M2-like TAMs. Consequently, the dual intervention of cancer cells and tumor microenvironment has become a research hotspot in the field of tumor immunotherapy. In this contribution, we developed pH-sensitive mesoporous calcium silicate nanocomposites (MCNs) encapsulated with indocyanine green (ICG) to enable the effective combination of photothermal therapy (PTT) and photodynamic therapy (PDT) triggered by the 808 nm near-infrared (NIR) light. The mannose and hyaluronic acid-grafted MCNs specifically targeted TAMs and tumor cells and promoted cell apoptosis both in vitro and in vivo. This paper revealed that irradiation of ICG loaded MCNs with NIR can produce a potent hyperthermia and induce abundant intracellular singlet oxygen generation in the target cells. These results suggest that the novel nanoplatform is believed to facilitate the delivery of chemotherapeutic agents to the tumor microenvironment (TME) to enhance the effects of tumor treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Destructive impacts of COVID-19 pandemic worldwide necessitates taking more appropriate measures for mitigating virus spread and development of the effective theranostic agents. In general, high heterogeneity of viruses is a major challenging issue towards the development of effective antiviral agents. Regarding the coronavirus, its high mutation rates can negatively affect virus detection process or the efficiency of drugs and vaccines in development or induce drug resistance. Bioengineered nanomaterials with suitable physicochemical characteristics for site-specific therapeutic delivery, highly-sensitive nanobiosensors for detection of very low virus concentration, and real-time protections using the nanorobots can provide roadmaps towards the imminent breakthroughs in theranostics of a variety of diseases including the COVID-19. Besides revolutionizing the classical disinfection procedures, state-of-the-art nanotechnology-based approaches enable providing the analytical tools for accelerated monitoring of coronavirus and associated biomarkers or drug delivery towards the pulmonary system or other affected organs. Multivalent nanomaterials capable of interaction with multivalent pathogens including the viruses could be suitable candidates for viral detection and prevention of further infections. Besides the inactivation or destruction of the virus, functionalized nanoparticles capable of modulating patient's immune response might be of great significance for attenuating the exaggerated inflammatory reactions or development of the effective nanovaccines and medications against the virus pandemics including the COVID-19., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Erythrocyte-mimicking nanovehicles (EM-NVs) are developed by fusing nanoparticle cores with naturally derived erythrocyte membranes. Compared with conventional nanosystems, EM-NVs hold preferable characteristics of prolonged blood circulation time and immune evasion. Due to the cell surface mimetic properties, along with tailored core material, EM-NVs have huge application potential in a large variety of biomedical fields, which are anticipated to revolutionize the present theranostic modalities of diseases in clinic. This review focuses on (I) drug carriers, (II) photosensitizers, (III) antidotes, (IV) vaccines and (V) probes, aiming to present an overall summary of the latest advancement in the application of EM-NVs, and highlight the major challenges and opportunities in this field., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Specific diagnosis and therapy of cancer is still a challenge in biomedical research. Photodynamic therapy (PDT) has emerged as a novel therapeutic modality for cancer treatment. However, the traditional PDT photosensitizers often exhibit low specific selectivity. In this study, we have reported a dual-targeted theranostic photosensitizer FL-RGD by covalently conjugating tumor marker cyclic arginine-glycine-aspartic acid tripeptide (RGD) and a fluorescein derivative FL which has a property of thermally activated delayed fluorescence (TADF) and a long triplet lifetime for efficient PDT. The FL-RGD can target tumor tissues and further locate lysosomes of tumor cells to concurrently achieve the cancers' specific diagnosis and efficient treatment. The mechanism of its highly efficient PDT was attributed to the damage of lysosome via 1 O 2 . Besides, FL-RGD has the potential to be utilized in depth imaging and treatment by two-photon excitation. The actual diagnosis performance of FL-RGD was proved by fluorescence imaging of living cells and tumor bearing mice. The therapy performance was proved by MTT assays, fluorescence-activated cell sorting (FACS) analysis and PDT experiments on tumor bearing mice. The research obviously exhibited the potential of FL-RGD for tumor theranostics in vivo and in vitro., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nanocarriers sensitive to near infrared light (NIR) are useful templates for chemo-photothermal therapy (PTT) and imaging of tumors due to the ability to change the absorbed NIR energy to heat. The conventional photo-absorbing reagents lack the efficient loading and release of drug before reaching the target site leading to insufficient therapeutic outcomes. To overcome these limitations, the surface of nanocarriers can be modified with different polymers with wide functionalities to provide systems with diagnostic, therapeutic, and theranostic capabilities. Among various polymers, polydopamine (PDA) has been more interested due to complex structure with various chemical moieties, and the capacity to be used through different coating mechanism. In this review, we describe the complex structure, chemical properties, and coating mechanisms of PDA. Moreover, the advantage and surface modification of some relevant nanosystems based on carbon materials, gold, iron oxide, manganese, and upconverting nanomaterials by using PDA will be discussed, in detail., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In recent years, novel two-dimensional (2D) nanomaterials are of great interest for diverse potential applications such as device fabrication, energy storage, sensing and theranostics because of their superlative physical features namely, large surface area, minimal thickness, tunable composition and easier surface modification methods. Rapid exploration in design and fabrication of 2D nano-structures have opened new avenue for cancer theranostics as it can encapsulate group of cancer cells and inflict major damage with great specificity in a non-invasive manner. Among the reported 2D materials such as graphene and its derivatives, metallic compounds, transition metal dichalcogenides (TMDC), black phosphorous and MXenes (e.g., carbides, nitrides, or carbonitrides), 2D nanomaterials based on graphene and TMDCs have gathered most of the limelight in this field due to their easily tunable properties. In this review, we summarize recent progress in the design of 2D theranostic nanomaterials, functionalization methods and their applications in photothermal therapy (PTT) as well as synergistic cancer therapy. We have also addressed the different modes of cellular entry of 2D nanomaterials into tumor cells based on their unique structural properties and investigated different methodologies to enhance PTT effect by optimizing the physico-chemical properties of the 2D sheets. Recent progress on in vitro and in vivo short and long term biocompatibility, immunotoxicity and excretion of the decorated structure is also highlighted. Investigation of the interaction of 2D nanomaterial with hematological factors such as RBC and WBC is of paramount importance as they are key indicators in in vivo responses, and this investigation will give a better solution for overcoming direct inflammation and infection related issues of the animal system. Besides, investigations on addressing the ways to incorporate polymer linkers and drug conjugates on to the surface of 2D materials, multiplexing capability, and the influence of surface functionalization on PTT effect is vital for future developments in clinical level diagnosis and cancer therapy. Finally, we conclude our opinion on current challenges and future prospective on meeting the various demands of advanced cancer imaging and therapies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Breakthroughs in clinical translation of cancer nanomedicine revolutionized smart theranostics approaches by addressing cancer heterogeneity using multifunctional treatment strategies. Geometrical anisotropy, supramolecular nanoarchitecture, and multiplex functionalities exemplified by various techniques incites the development of integrated multi-modal drug delivery systems for circulating tumor clusters (CTC). Average survival rate of the patients with locally advanced tumor demands the intelligent theranostic system to control the primary progression, invasion and extravasation of CTCs. However, rapid elimination of these highly aggressive and metastatic clusters of tumor cells disseminated in blood, prior to soiling at new distant sites, would increase the lifespan of the patients. This review provides insight on RSSR (Retention, Stealth, Sticky, and Release) strategy for engineering smart hybrid nanostructures to target CTC and thereby terminate the metastatic cascade before formation of secondary niches., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent interest in triblock dendritic unimolecular micelles has opened a new spectrum for its ubiquitous application in biomedical sciences specially drug delivery. Unimolecular dendritic micelles have brought significant attention due to their high encapsulation efficiency, high-functionality, and site specific confinement capabilities. During the last decade, the number of publications in this field has increased drastically, reinforced by the fact that several clinical trials are underway using micelles for drug delivery. This review unveils the most recent advancement on the synthesis and applications of cutting-edge unimolecular micelles using dendritic and star-shaped molecules emphasizing on triblock copolymers. The major biomedical applications covered in this manuscript are drug/gene/bio-macromolecules delivery to the site of interest, as contrast agents in bio-imaging, and cancer targeted theranostics using stimuli-responsive mechanism., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lung cancer is the foremost reason of death from cancers with broad genetic and epigenetic diversity. Various strategies are clinically available for diagnosis and treatment of lung cancer. However, in many cases, the disease is diagnosed after malignancy that reduce the survival rate of lung cancer patients due to unsuccessful response to therapy. With the help of nanotechnology, various nanoparticulate systems including organic, inorganic, metallic, and polymeric nanoparticles have been developed for diagnosis and treatment of lung cancer. Each of these nanocarriers possess their own advantages and disadvantages. Combining the organic and inorganic components in a single hybrid nanosystem prepares a new generation of multifunctional nanoparticles with enhanced structural and biological properties. Such nanoparticles not only have beneficial features of all the bulk materials, but also can be tuned in terms of structural and functional moieties to provide carriers with improved diagnostic and therapeutic outcomes. Indeed, hybrid nanoparticles with the ability to incorporate multiple drugs, targeting agents, and photosensitive reagents opened new insights into developing more sensitive and specified systems for diagnosis and treatment of lung cancer compared with conventional nanocarriers. In this review, recent developments in designing different hybrid nanoparticles with diagnostic, therapeutic, and theranostic properties for lung cancer are explained in detail., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Drug delivery systems are entities designed to alter the biological behaviour of the pharmaceutical active ingredients that they carry in order to afford more beneficial biodistribution and safety profiles. Many problems currently faced by the field of nuclear medicine (e.g. developing new theranostic agents, utilizing multimodal imaging platforms and providing targeted delivery) can be facilitated by applying drug delivery systems to radiopharmaceuticals that have been proven successful in other medical fields. This review describes the advancements being made towards this goal., Areas Covered: All aspects of drug delivery systems (liposomes, nanoparticles, microspheres) in the field of nuclear medicine are discussed. Only systems with foreseen or confirmed clinical applications in nuclear medicine are discussed, not instances where nuclear imaging is merely a tool to evaluate the biodistribution of novel delivery technologies., Conclusion: Great advancements have been made with the development of novel systems incorporating nuclear entities in drug delivery systems, with the possibility of reshaping the nuclear medicine landscape. Nonetheless, translation from preclinical evaluations to clinical use is lacking and serious investment needs to be made towards this goal., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Large surface area, uniform and tunable pore size, high pore volume and low mass density- such attractive features of Mesoporous silica nanoparticles (MSNPs) have compelled researchers to explore the biomedical potential of this nano-material. Recently gained interest in MSNPs have been due to their tremendous potential in cancer therapy and imaging. Last several years have witnessed a rapid development in engineering functionalized MSNPs with various types of functional groups integrated into the system for imaging and therapeutic applications. Although their potential for drug delivery application has been studied since the year 2000, still a major challenge is to improve drug loading capacity and in vivo targeting with minimal side-effects to major organs. In this review article, the recent development of MSNPs as a therapeutic and diagnostic platform has been detailed out with emphasis on drug and bio-macromolecule delivery/co-delivery, bio-imaging and detoxification., (Copyright © 2018 Elsevier B.V. All rights reserved.)

For the purpose of precision theranostic of tumor, multifunctional drug delivery systems are always receiving great attentions. Here, we developed a zinc phthalocyanine-soybean phospholipid (ZnPc-SPC) complex based drug delivery system with doxorubicin (Dox) as loading cargo to achieve additional chemotherapy while the carrier itself could serve as multifunctional and switchable theranostic agent. In the early phase, the ZnPc-SPC complex assembled to nanostructure displaying photothermal therapy (PTT) and photoacoustic (PA) properties while in the late phase, the prepared NPs dis-assembled into ZnPc-SPC complex again performing photodynamic therapy (PDT) and low-background fluorescence (FL) image. With the decoration of folate receptors α (FRα) targeted MTX, Dox-loaded, MTX-decorated self-assembled ZnPc-SPC complex NPs (DZSM) was formed. In vitro and in vivo evaluations both indicated that DZSM presented high selectivity for FRα over-expressed tumor cells, excellent switchable PA/FL image, significant multiphase PTT/PDT effect, as well as great synergetic therapy potential, leading to notable inhibition of tumor growth., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Adipose-derived stem cells (ADSCs) have been utilized in cellular delivery systems to carry therapeutic agents into tumors by migration. Drug-loaded nanodroplets release drugs and form bubbles after acoustic droplet vaporization (ADV) triggered by ultrasound stimulation, providing a system for ultrasound-induced cellular delivery of theranostic agents. In order to improve the efficiency of drug release, fusogenic nanodroplets were designed to go from nano to micron size upon uptake by ADSCs for reducing ADV threshold. The purpose of our study was to demonstrate the utility of camptothecin-loaded fusogenic nanodroplets (CPT-FNDs) as ultrasound theranostic agents in an ADSCs delivery system. CPT-FNDs showed an increase in size from 81.6 ± 3.5 to 1043.5 ± 28.3 nm and improved CPT release from 22.0 ± 1.8% to 37.6 ± 2.1%, demonstrating the fusion ability of CPT-FNDs. CPT-FNDs-loaded ADSCs demonstrated a cell viability of 77 ± 4%, and the in vitro migration ability was 3.2 ± 1.2-fold for the tumor condition compared to the cell growth condition. Ultrasound enhancement imaging showed intratumoral ADV-generated bubble formation (increasing 3.24 ± 0.47 dB) triggered by ultrasound after CPT-FNDs-loaded ADSCs migration into B16F0 tumors. Histological images revealed intratumoral distribution of CPT-FNDs-loaded ADSCs and tissue damage due to the ADV. The CPT-FNDs can be used as theranostic agents in an ADSCs delivery system to provide the ultrasound contrast imaging and deliver combination therapy of drug release and physical damage after ADV., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The size of nanoparticles plays a key role in utilizing enhanced permeability and retention (EPR) effect of tumor, where large-sized nanoparticles possess good retention but poor penetration, while small-sized nanoparticles are on the contrary. Although size-reducible nanoparticles have been designed to partially overcome this dilemma, the initial size and complicated tumor microenvironment remain restricting the tumor distribution of nanoparticles. Herein, we employed tumor-specific CD44 targeted, hyaluronidase-degradable hyaluronic acid (HA) and small-sized, renal-clearable, red emission, cationic bovine serum albumin-protected gold nanocluster (AuNC@CBSA) to successfully construct size-reducible nanoplatform (AuNC@CBSA@HA). By changing the ratio of HA and AuNC@CBSA, different initial sizes of AuNC@CBSA@HA were prepared and their tumor targeting efficiencies, pharmacokinetic profiles were evaluated. Then 200 nm of AuNC@CBSA@HA with optimal EPR effect was screened out to further load paclitaxel (PTX) and indocyanine green (ICG) for chemo- photothermal therapy and nitric oxide (NO) for modulating tumor microenvironment and enhancing drug delivery. The AuNC@CBSA-PTX-ICG@HA-NO 3 showed size-reducible ability under triggering by hyaluronidase and high accumulation in breast cancer with homogenous intra-tumor distribution, suppressed 95.3% of in-situ tumor growth and inhibited 88.4% of lung metastasis growth. In conclusion, we provide a strategy that fully satisfied the concerns in drug delivery to tumor for improved antitumor effect., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Multimodal imaging-guided synergistic combination therapy has shown great potential for cancer treatment. However, the nanocarrier-based theranostic systems suffer from batch-to-batch variation, complexity of multicomponent, poor drug loading, and carrier-related toxicity issues. To address these issues, herein we developed a novel carrier-free theranostic system with nanoscale characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging-guided synergistic chemo-photothermal therapy (PTT). Indocyanine green (ICG) and epirubicin (EPI) could co-self-assemble into small molecular nanoparticles (NPs) in aqueous solution without any molecular precursor or excipient via collaborative interactions (electrostatic, π-π stacking, and hydrophobic interactions). The exceptionally high dual-drug loading (∼92wt%) ICG-EPI NPs showed good physiological stability, preferable photothermal response, excellent NIRF/PA imaging properties, pH-/photo-responsive drug release behavior, and promoted cellular endocytosis compared with free ICG or EPI. Importantly, the ICG-EPI NPs showed excellent tumor targeting ability with high spatial resolution and deep penetration via in vivo NIRF/PA dual-modal imaging. Moreover, in comparison with individual chemotherapy or PTT, the combinational chemo-PTT therapy of ICG-EPI NPs with NIR laser irradiation synergistically induced apoptosis and death of cancer cells in vitro, and showed synergistic chemo-PTT efficiency in vivo as evidenced by highly efficient tumor ablation. Furthermore, the ICG-EPI NPs exhibited inappreciable toxicity. This co-self-assembly of both FDA-approved agents provides a safe and "Molecular economical" strategy in the rational design of multifunctional nano-theranostic systems for real-time self-monitoring intracellular drug delivery and targeting multimodal imaging-guided synergistic combination therapy., (Copyright © 2017. Published by Elsevier B.V.)

Recently, a great interest has been paid to the development of hybrid protein-inorganic nanoparticles (NPs) for drug delivery and cancer diagnostics in order to combine the merits of both inorganic and protein nanocarriers. This review primarily discusses the most outstanding advances in the applications of the hybrids of naturally-occurring proteins with iron oxide, gadolinium, gold, silica, calcium phosphate NPs, carbon nanotubes, and quantum dots in drug delivery and cancer imaging. Various strategies that have been utilized for the preparation of protein-functionalized inorganic NPs and the mechanisms involved in the drug loading process are discussed. How can the protein functionalization overcome the limitations of colloidal stability, poor dispersibility and toxicity associated with inorganic NPs is also investigated. Moreover, issues relating to the influence of protein hybridization on the cellular uptake, tumor targeting efficiency, systemic circulation, mucosal penetration and skin permeation of inorganic NPs are highlighted. A special emphasis is devoted to the novel approaches utilizing the protein-inorganic nanohybrids in combined cancer therapy, tumor imaging, and theranostic applications as well as stimuli-responsive drug release from the nanohybrids., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentially overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. The modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Layer-by-layer (LbL) based self-assembly of nanoparticles is an emerging and powerful method to develop multifunctional and tissue responsive nanomedicines for a broad range of diseases. This unique assembly technique is able to confer a high degree of modularity, versatility, and compositional heterogeneity to nanoparticles via the sequential deposition of alternately charged polyelectrolytes onto a colloidal template. LbL assembly can provide added functionality by directly incorporating a range of functional materials within the multilayers including nucleic acids, synthetic polymers, polypeptides, polysaccharides, and functional proteins. These materials can be used to generate hierarchically complex, heterogeneous thin films on an extensive range of both traditional and novel nanoscale colloidal templates, providing the opportunity to engineer highly precise systems capable of performing the numerous tasks required for systemic drug delivery. In this review, we will discuss the recent advancements towards the development of LbL nanoparticles for drug delivery and diagnostic applications, with a special emphasis on the incorporation of biostability, active targeting, desirable drug release kinetics, and combination therapies into LbL nanomaterials. In addition to these topics, we will touch upon the next steps for the translation of these systems towards the clinic., (Copyright © 2016. Published by Elsevier B.V.)

Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this study, an organic-inorganic hybrid nanocomposite was synthesized by deposition of Au onto the surface of docetaxel (DTX)-loaded poly (lactide-co-glycolide) (PLGA) nanoparticle cores to form the core-shell structured DTX-loaded PLGA@Au nanoparticles. The tumor targeting peptide, angiopep-2, was then introduced onto the gold nanoshell through Au-S bond, achieving drug delivery with active targeting capability. This novel system allowed combined chemotherapy and thermal therapy for cancer, resulting from DTX and gold nanoshell. The formation of tumor-targeting gold nanoshell surrounding PLGA nanocore, designated as ANG/GS/PLGA/DTX NPs, was confirmed by its surface plasmon resonance (SPR) band in the UV-Vis spectrum and by a transmission electron microscope (TEM). The release profiles of DTX from this system showed strong dependence on near-infrared (NIR) laser. Compared with DTX alone, the ANG/GS/PLGA/DTX NPs afforded much higher anti-tumor efficiency without obvious toxic effects. Besides, it also showed potential X-ray imaging ability. These results demonstrated that the tumor-targeting core-shell structured DTX-loaded PLGA@Au nanoparticles could be used as a multifunctional nanomaterial system with NIR-triggered drug-releasing properties for tumor-targeted chemo-photothermal therapy and theranostics., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Photoacoustic imaging is the latest promising diagnostic modality that has various advantages such as high spatial resolution, deep penetration depth, and use of non-ionizing radiation. It also employs a non-invasive imaging technique and optically functionalized imaging. The goal of this study was to develop a nanomedicine for simultaneous cancer therapy and diagnosis based on photoacoustic imaging. Human serum albumin nanoparticles loaded with melanin and paclitaxel (HMP-NPs) were developed using the desolvation technique. The photoacoustic-based diagnostic and chemotherapeutic properties of HMP-NPs were evaluated through in vitro and in vivo experiments. The size and zeta potential of the HMP-NPs were found to be 192.8±21.11nm and -22.2±4.39mV, respectively. In in vitro experiments, HMP-NPs produced increased photoacoustic signal intensity because of the loaded melanin and decreased cellular viability because of the encapsulated paclitaxel, compared to the free human serum albumin nanoparticles (the control). In vivo experiments showed that the HMP-NPs efficiently accumulated inside the tumor, resulting in the enhanced photoacoustic signal intensity in the tumor site, compared to the normal tissues. The in vivo chemotherapy study demonstrated that HMP-NPs had the capability to treat cancer for an extended period. In conclusion, HMP-NPs were simultaneously capable of photoacoustic diagnostic and chemotherapy against cancer., (Copyright © 2015 Elsevier B.V. All rights reserved.)