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Gynecological inflammations have a significant impact on the daily lives of women. Meanwhile, cancers such as ovarian, cervical, and endometrial cancers pose severe threats to their physical and mental well-being. While current options such as conventional pharmacotherapy, surgical interventions, and recent advancements in immunotherapy and targeted therapy provide viable solutions, they possess limitations in effectively addressing the intricacies associated with gynecological diseases. These complexities include post-surgical complications, early cancer detection, and drug resistance. The management of these challenges, however, requires the implementation of innovative treatment modalities. Phototheranostics has emerged as a promising approach to effectively address these challenges. It not only treats inflammation and tumors efficiently but also aids in disease imaging and diagnosis. The distinguishing features of phototheranostics lie in their non-invasive nature, minimal risk of drug resistance, and precise targeting capabilities through the use of photosensitizers or photothermal agents. These distinctive features underscore its potential to revolutionize early diagnosis and treatment of gynecological conditions. This review aims to summarize the application of phototheranostics in managing gynecological inflammation and tumors while highlighting its significant potential for early disease detection and treatment., 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 Ltd. All rights reserved.)

The healing of chronic wounds infected by bacteria has attracted increasing global concerns. In the past decades, antibiotics have certainly brought hope to cure bacteria-infected chronic wounds. However, the misuse of antibiotics leads to the emergence of numerous multidrug-resistant bacteria, which aggravate the health threat to clinical patients. To address these increasing challenges, scientists are committed to creating novel non-antibiotic strategies to kill bacteria and promote bacteria-infected chronic wound healing. Fortunately, with the quick development of nanotechnology, the representatives of phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit promising possibilities in promoting bacteria-infected wound healing. Well-known, photothermal agents and photosensitizers largely determine the effects of PTT and PDT. A common problem for these molecules is the aggregation-induced quenching effect, which highly limits their further applicability in biomedical and clinical fields. Fortunately, the occurrence of aggregation-induced emission luminogens (AIEgens) efficiently overcomes the photobleaching and exhibit advantages, such as strongly aggregated emission, superior photostability, aggregation-enhanced reactive oxygen species (ROS), and heat generation, which makes great sense to the development of PTT and PDT. This article reviews various studies conducted on novel AIEgen-based materials that can mediate potent PDT, PTT, and a combination of PDT and PTT to promote bacteria-infected chronic wound healing., 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 Ltd. All rights reserved.)

Multifunctional nanoplatforms capable of simultaneously executing multimodal therapy and imaging functions are of great potentials for cancer theranostics. We present an elegantly designed, easy-to-fabricate poly(acrylic acid)/mesoporous calcium phosphate/mesoporous copper phosphate nanosphere (PAA/mCaP/mCuP NS) with outstanding pH/NIR-sensitive multimodal-synergic anti-tumor effects. Optimal porous PAA NS scaffolds were prepared at room temperature by balancing the intra-PAA polymer and polymer-solvents Lennard-Jones potentials in a water:isopropyl alcohol (IPA) mix-solvent. Subsequent sponging of Ca 2+ and Cu 2+ , and adsorption of PO 4 3- to the PAA template were achieved through exquisite electrostatic interactions among ions and the ionizable PAA side-chain in an aqueous environment. This forms the basis for the tumor microenvironment pH-triggered release of Cu 2+ to induce cuproptosis, as well as the photothermal effect originating from CuP, while Ca 2+ can enhance the nanoplatform's biocompatibility and can damage mitochondria when overloaded. Lastly, PAA/mCaP/mCuP NSs still exhibit high drug loading efficiency for doxorubicin (DOX), enabling chemotherapy. Satisfactory anti-tumor effects of these modalities, along with their synergistic effects, were verified both in vitro and in vivo, with the NSs demonstrating good biodegradation in the latter. The fabricated NS itself holds great promise as an anti-tumor nanomedicine, and the thorough mechanical insights into NS formation may inspire the design of next-generation multifunctional nanoplatforms., 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 Ltd. All rights reserved.)

Inflammatory bowel disease (IBD) is characterized by the upregulation of reactive oxygen species (ROS) and dysfunction of gut immune system, and microbiota. The conventional treatments mainly focus on symptom control with medication by overuse of drugs. There is an urgent need to develop a closed-loop strategy that combines in situ monitoring and precise treatment. Herein, we innovatively designed the 'cluster munition structure' theranostic microgels to realize the monitoring and therapy for ulcerative colitis (a subtype of IBD). The superoxide anion specific probe (tetraphenylethylene-coelenterazine, TPC) and ROS-responsive nanogels consisting of postbiotics urolithin A (UA) were loaded into alginate and ion-crosslinked to obtain the theranostic microgels. The theranostic microgels could be delivered to the inflammatory site, where the environment-triggered breakup of the microgels and release of the nanogels were achieved in sequence. The TPC-UA group had optimal results in reducing inflammation, repairing colonic epithelial tissue, and remodeling microbiota, leading to inflammation amelioration and recovery of tight junction between the colonic epithelium, and maintenance of gut microbiota. During the recovery process, the local chemiluminescence intensity, which is proportional to the degree of inflammation, was gradually inhibited. The cluster munition of theranostic microgels displayed promising outcomes in monitoring inflammation and precise therapy, and demonstrated the potential for inflammatory disease management., 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 Ltd. All rights reserved.)

Organic photosensitizers (PSs) play important roles in phototheranostics, and contribute to the fast development of precision medicine. However, water-soluble and highly emissive organic PSs, especially those emitting in the short-wave infrared region (SWIR), are still challenging. Also, it's difficult to prepare self-reporting PSs for visualizing the treatment via stimulated emission depletion (STED) nanoscopy. Thus, in this work, a water-soluble molecule of DTPAP-TBZ-I with aggregation-induced emission features is designed for the self-reporting photodynamic therapy (PDT) in an ultra-high resolution. In contrast to single molecule, its complex (DTPAP-TBZ-I@BSA) shows much enhanced fluorescence properties and reactive oxygen species (ROS) generation in SWIR window. Their photoluminescence quantum yield is determined to be ∼20.6 % and the enhancement of ROS generation is ∼18-fold. During the PDT, immigration of the complex from cytoplasm to nucleus is also observed via STED nanoscopy with a resolution of 66.11 nm, which allows self-report in the PDT treatment. DTPAP-TBZ-I@BSA is finally utilized for the imaging-guided PDT in vivo with a tumor inhibition rate of 84 %. This is the first work in albumin-enhanced water-soluble organic PSs in SWIR window for self-reporting phototheranostics at ultra-high resolutions, providing an ideal solution for the next generation of photosensitizers for precise medicine., 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 Ltd. All rights reserved.)

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements. The resulting nanocomposite can tightly bind to fungal surfaces, promote DNA recognition, and squeeze pro-inflammatory cytokines to relieve inflammation. Consequently, this nanocomposite can detect C. albicans with enhanced sensitivity and precisely eliminate fungal cells through photodynamic therapy with minimal phototoxicity because of its switchable fluorescence behavior. The developed nanocomposite with good biocompatibility achieves a satisfactory diagnostic and therapeutic effect in a C. albicans-infected mouse model, which offers a unique approach to fight fungi infection., 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 Ltd. All rights reserved.)

Optically active organic nanoparticles capable of emitting strong near-infrared II (NIR-II) fluorescence and eliciting tumor hyperthermia are promising for tumor imaging and photothermal therapy (PTT). However, their applications for the treatment of pancreatic tumors via mere PTT are challenging as both the nanoparticles and light are hard to enter the deeply located pancreatic tumors. Here, we report a NIR-II light excitable, carbonic anhydrase (CA)-targeting cisplatin prodrug-decorated nanoparticle (IRNPs-SBA/Pt IV ) for NIR-II fluorescence imaging (FLI)-guided combination PTT and chemotherapy of pancreatic tumors. IRNPs-SBA/Pt IV is designed to hold a high photothermal conversion efficiency (PCE ≈ 65.17 %) under 1064 nm laser excitation, a strong affinity toward CA (K d  = 14.40 ± 5.49 nM), and a prominent cisplatin release profile in response to glutathione (GSH) and 1064 nm laser irradiation. We show that IRNPs-SBA/Pt IV can be actively delivered into pancreatic tumors where the CA is upregulated, and emits NIR-II fluorescence to visualize tumors with a high sensitivity and penetration depth under 980 nm laser excitation. Moreover, the tumor-resided IRNPs-SBA/Pt IV can efficiently inhibit the CA activity and consequently, relieve the acidic and hypoxic tumor microenvironment, benefiting to intensify chemotherapy. Guided by the NIR-II FLI, IRNPs-SBA/Pt IV is capable of efficiently inhibiting pancreatic tumor growth via combinational PTT and chemotherapy with 1064 nm laser excitation under a low-power density (0.5 W cm -2 , 10 min). This study demonstrates promise to fabricate NIR-II excitable nanoparticles for FLI-guided precise theranostics of pancreatic tumors., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Multimodal phototheranostics on the basis of single molecular species shows inexhaustible and vigorous vitality, particularly those emit fluorescence in the second near-infrared window (NIR-II), the construction of such exceptional molecules nonetheless retains formidably challenging. In view of the undiversified molecular skeletons and insufficient phototheranostic outputs of previously reported NIR-II fluorophores, herein, electron acceptor engineering based on heteroatom-inserted rigid-planar pyrazinoquinoxaline was manipulated to fabricate aggregation-induced emission (AIE)-featured NIR-II counterparts with donor-acceptor-donor (D-A-D) architecture. Systematical investigations substantiated that one of those synthesized AIE molecules, namely 4TPQ, incorporating a fused thiophene acceptor, synchronously exhibited high molar absorptivity (ε), NIR-II emission, typical AIE tendency, significant reactive oxygen species (ROS) generation, and high photothermal conversion efficiency. These extraordinary behaviors endowed 4TPQ nanoparticles with unprecedented performance on NIR-II fluorescence/photothermal imaging-navigated synergistic photodynamic/photothermal inhibition of tumors, as confirmed by the mice model of breast cancer bone metastases. This study thus brings significant insights into developing phototheranostic systems for clinical trials., 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 Elsevier Ltd. All rights reserved.)

In vivo monitoring of treatment response is of great significance for tumor therapy in clinical trials, but it remains a formidable challenge. Herein, we demonstrate a logic AND gate theranostic nanoagent that responds to the coexistence of endogenous and exogenous stimuli, namely HAuCl 4 @1-Tetradecanol@Gd-based metal-organic framework@SiO 2 nanocomposites (APGS NCs). Upon microwave (MW) irradiation, HAuCl 4 in the inner part of APGS NCs reacts with the tumor-associated glutathione (GSH). Subsequently, it transforms into an active luminescent form of Au@1-Tetradecanol@Gd-MOF@SiO 2 nanocomposites (AuPGS NCs). The intensity of generated fluorescence is correlated with the tumor thermal-injury status. Thus, the generation of AuPGS NCs with high intensity fluorescence under the co-activation of MW and GSH can visualize the treatment effects during MW thermal therapy and instantly modulate the irradiation time and range for optimal outcomes. Hence, this logic gate controlled APGS NCs makes MW thermal therapy eliminate tumor cells completely. This research offers an effective strategy for the design and preparation of activatable theranostic nanoagents for precise tumor imaging and therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xianwei Meng, Ping Liang reports financial support was provided by National Natural Science Foundation of China. Jun Ren reports financial support was provided by Beijing Natural Science Foundation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Due to the aggregation-caused quenching (ACQ) and weak photo-penetrating ability, the application of phototheranostic agents in drug delivery field is greatly limited. Ferroptosis, a newly discovered cell death mode, has not been extensively studied in the field of phototherapy up to now. Here, a new near-infrared II (NIR-II) molecule with aggregation-induced emission (AIE) property (named TSST) co-assembled with DHA-PEG and ferrocene as nanoparticles (DFT-NP), which was rationally designed and synthesized. The DFT-NP exhibited enhanced NIR-II fluorescence, photothermal, photoacoustic, magnetic resonance imaging, AIE and ferroptosis capacities. The NIR-II fluorescence intensity of obtained nanoparticles was improved, owing to the strong interaction between DHA and TSST, which limited the intramolecular rotation restriction and non-radiative attenuation of TSST to discourage energy dissipation in aggregation state. Inspiringly, the generated photothermal effect by DFT-NP can promote the Fenton reaction of ferrocene and H 2 O 2 , resulting in dissolution of the nanoparticles and cancer cells expedited ferroptosis via accumulation lipid free radicals of DHA. The released TSST enhanced the photothermal and photoacoustic imaging effects through removing the DHA restriction to restore the non-radiative attenuation. This work is the first example of nanoparticles that integrates four-mode imaging, photothermal and ferroptosis-induced therapy functions, which offers great advantages for potential clinical applications., 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 © 2022. Published by Elsevier Ltd.)

Bacterial infection is the leading cause of many serious inflammation diseases threatening human health. Existing theranostic options for bacterial infection are always complicated and unsatisfactory. There is an increasing interest in developing a more effective theranostic approach for the treatment of infections. Herein, we report the development of a near-infrared (NIR) chemiluminescent (CL) nanoparticles ALPBs containing luminol, AIE dye (TTDC), PCPDTBT, and nitric oxide (NO) donor (BNN6), which could achieve a deep CL imaging-guided photothermal-NO gas therapy of bacterial infection. After intravenous injection, ALPBs could be largely accumulated in the infected site and then activated by oversecreted reactive oxygen species (ROS) to produce near-infrared chemiluminescence, which could precisely track infection-induced local inflammation. Under the guidance of imaging, synergistic photothermal-NO therapy was further performed by 808 nm laser irradiation, leading to active bacterial eradication and rapid recovery of infected tissues. The utility of ALPBs provides a powerful and controllable "all-in-one" platform for combating bacterial infection., 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 © 2022. Published by Elsevier Ltd.)

While the miniaturization and motility of artificial nanomotors made them popular tools for exploring novel and innovative biomedical cancer treatment strategies, the integration of multiple functions on the small motor bodies is key to achieve further progress but remains unresolved. Here, we propose a dual-source powered Janus nanomotor whose composition integrates multiple photo-theranostic functions such as surface-enhanced Raman scattering (SERS) sensing, fluorescence imaging/photoacoustic imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). This nanomotor can be fabricated by sputtering a thin gold layer onto one side of mesoporous silica (mSiO 2 ) combined with surface modification by photo-sensitizer, Raman reporter, and catalase. Upon illumination with 808 nm near-infrared light, the half-coated gold nanoshell serves as PAI/PTT agent, and by upconverting NIR to visible light, the pre-loaded photosensitizer can be excited by the upconverted light of UCNPs to convert the dissolved oxygen (O 2 ) into reactive oxygen species for efficient PDT. Furthermore, ratiometric SERS signal can be captured to quantitatively detect the tumor marker, H 2 O 2 , in cellular microenvironments. The immobilized catalase as a nano-engine can catalyze endogenous H 2 O 2 to O 2 . This function not only improves the hypoxic tumor microenvironment and therefore enhances PDT efficiency, but also provides a thrust force for deep penetration. As a proof of concept for the in vivo trial we performed cancer photo-theranostics where our nanomotors successfully treated a mouse breast tumor in a subcutaneous tumor model. The results are promising and encourage the use of an integrated nanomotor platform that could be further developed into a photo-theranostic agent for superficial cancer treatment., 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 © 2022 Elsevier Ltd. All rights reserved.)

As one of the major public health concerns, malignant tumors threaten people's lives. With the increasing demand for early accurate diagnosis and the safe treatment of tumors, non-invasive optical imaging (including fluorescence imaging and photoacoustic imaging) and phototherapy (including photothermal therapy and photodynamic therapy) have received much attention. In particular, light in the near-infrared second region (NIR-II) has been attracting research interest, owing to its deep penetration, minimal tissue autofluorescence, and decreased tissue absorption and scattering. Among all biological materials, organic nanomaterials with aggregation-induced emission (AIE) properties have attracted significant attention, owing to various incomparable advantages, such as high brightness, good photostability, tunable photophysical properties, and good biosafety. To modulate the working optical region of AIE molecules to the NIR-II region, many researchers have tried a variety of methods in recent years, and the focus of this review is to summarize the three most common methods from the perspective of molecular design strategies. In addition, this article briefly reviews the recent five-year progress of NIR-II AIE luminophores in tumor imaging and phototherapy applications. The research status is also summarized and prospected, with the hope of contributing to further research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In view of the fact that pancreatic cancer, called as the king of cancer, is one of the most lethal malignancies, exploring effective technologies for pancreatic cancer diagnosis and therapy remains an appealing yet significantly challenging task. Phototheranostics has recently received considerable attention by virtue of its various distinctive advantages. However, the limited penetration depth, strong oxygen-dependence and high heat shock protein-inhibition of conventional phototheranostic materials severely hamper their overall theranostic efficacy, especially for deep-seated hypoxia tumors, such as pancreatic tumor. In this study, an aggregation-induced emission (AIE)-featured photosensitizer, namely DCTBT, synchronously sharing NIR-II fluorescence imaging (FLI), diminished oxygen-dependent type-I photodynamic therapy (PDT) and high-efficiency photothermal therapy (PTT) functions was subtly constructed by molecular engineering. With the aid of an EGFR-targeting-peptide-modified amphiphilic polymer, the as-prepared DCTBT-loaded liposomes is capable of effectively accumulating at and visualizing pancreatic tumor, as well as significantly suppressing the tumor growth on both subcutaneous and orthotopic PANC-1 tumor mice models. This study thus brings useful insights into designing the next generation of cancer theranostic agents for potential clinical applications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

As a chronic and lifelong disease, obesity not only significant impairs health but also dramatically shortens life span (at least 10 years). Obesity requires a life-long effort for the successful treatment because a number of abnormalities would appear in the development of obesity. Nanomaterials possess large specific surface area, strong absorptivity, and high bioavailability, especially the good targeting properties and adjustable release rate, which would benefit the diagnosis and treatment of obesity and obesity-related metabolic diseases. Herein, we discussed the therapy and diagnosis of obesity and obesity-related metabolic diseases by using nanomaterials. Therapies of obesity with nanomaterials include improving intestinal health and reducing energy intake, targeting and treating functional cell abnormalities, regulating redox homeostasis, and removing free lipoprotein in blood. Diagnosis of obesity-related metabolic diseases would benefit the therapy of these diseases. The development of nanomaterials will promote the diagnosis and therapy of obesity and obesity-related metabolic diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Natural particles ranging from various cell membranes to nascent proteins are highly optimized for their specific functions in vivo and possess features that are desired in drug delivery carriers. However, the current endeavor in research on bioparticles is still seeking the appropriate strategy to shield multiple agents and circumvent biological hurdles. These issues have propelled the advancement of lipid-polymer hybrid nanocarriers, which could be employed as drug reservoirs and strive to meet these expectations. We thereby proposed functionalized biopeptide-lipid hybrid particles, which were applied to encapsulating a PLGA polymeric core together with indocyanine green (ICG) and packaged by a lipoprotein-inspired structural shell. To initiate precision tumor-penetrating performance, tLyP-1-fused apolipoprotein A-I-mimicking peptides (D4F) were exploited to impart tumor-homing and tumor-penetrating biological functions. The sub-100 nm drug vehicle possessed a long circulation time with uniform mono-dispersity but was stable enough to navigate freely, penetrate deeply into tumors and deliver its cargoes to the targeted sites. Moreover, ICG-encapsulated penetrable polymeric lipoprotein particles (PPL/ICG) could realize real-time fluorescence/photoacoustic imaging for monitoring in vivo dynamic distribution. Upon near-infrared (NIR) laser irradiation, PPL/ICG demonstrated a highly efficient phototherapeutic effect to eradicate orthotopic xenografted tumors, resulting in an 88.77% decrease from the initial tumor volume and inhibited tumor metastasis with good biosafety. Therefore, the described bio-strategy opens new avenues for creating polymeric lipoproteins with varied hybrid functionalities, which may be applied to provide a basis and inspiration for improved nanoparticle-based precision theranostic nanoplatforms., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Targeted activation or enhancement is an attractive strategy in the design of nano-theranostics. However, the responsiveness of the nanoagents is restricted by the limited levels of intra-tumor stimuli. Herein, we constructed a positive feedback nanoamplifier by encapsulating glucose oxidase (GOx) in the ferric ions contained metal organic framework (MIL-100), and coating the nanoparticles with polydopamine modified hyaluronic acid (HA-PDA). The mechanism of action of the ensuing nanoamplifiers was three pronged: 1) the high intra-tumor acidity accelerated the release of GOx, which consumed endogenous glucose and "starved" the tumors, in addition to aggravating the local acidity and H 2 O 2 levels; 2) the hydroxyl radicals (·OH) generated from the Fenton-like reaction between MIL-100 with H 2 O 2 contributed to the chemodynamic tumor therapy and augmented the O 2 microenvironment, which could be speeded up under acid condition; 3) the oxygen (O 2 ) produced in the Fenton-like reaction relieved the intra-tumor hypoxia and ensured the enzymatic reaction of GOx, along with augmenting the photoacoustic signal of nanoamplifier. Preliminary experiments in tumor bearing mice showed that the nanoamplifier not only boosted the local acidity/H 2 O 2 /O 2 levels in tumor site to successfully suppress the growth of tumors through the self-enhanced chemodynamic/starving therapy, but also achieved the photoacoustic imaging of tumors. Taken together, this novel nanoamplifier with the abilities of self-enhanced tumor imaging and therapy is a promising entrant in the field of anti-tumor theranostics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A tumor-related stimuli-activatable and biodegradable nanoplatform for tumor-selective imaging and effective photodynamic therapy (PDT) towards precision medicine is highly desirable but still greatly challenging. Here, we developed a novel H 2 O 2 -activatable and biodegradable nanomedicine (BSA-MBPB) by encapsulation of a single newly synthesized pro-photosensitizer (MBPB) with its photoactivity completely annihilated within bovine serum albumin (BSA) to achieve imaging-guided tumor-targeted effective PDT. BSA-MBPB can be decomposed and activated by H 2 O 2 to not only produce the clinical photosensitizer methylene blue to recover its fluorescent, photoacoustic and photosensitizing properties for dual-modal imaging and cytotoxic singlet oxygen ( 1 O 2 ) generation, but also to simultaneously produce a GSH-depleting adjuvant quinone methide to boost the 1 O 2 yield, thus strengthening the efficacy of PDT. BSA-MBPB allows for highly efficient and accurate PDT without major side effects, offering potential as the next-generation nanomedicine towards clinical practice of precise PDT., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hypoxia plays vital roles in the development of tumor resistance against typical anticancer therapies and local reoxygenation has proved effective to overcome the hypoxia-induced chemoresistance. Perfluorocarbon (PFC) is an FDA approved oxygen carrier and currently vigorously investigated for oxygen delivery to tumors. This study reports a perfluorocarbon and etoposide (EP) loaded porous hollow Fe 3 O 4 -based theranostic nanoplatform capable of delivering oxygen to solid tumors to enhance their susceptibility against EP. Results show that oxygen could be released at a moderate rate from the porous hollow magnetic Fe 3 O 4 nanoparticles (PHMNPs) over an extended period of time, therefore effectively reducing the hypoxia-induced EP resistance of tumor cells. Moreover, the surface of PHMNPs was modified with lactobionic acid (LA)-containing amphiphilic polymers via hydrophobic interaction, which could provide targeting effect against certain types of tumors. The hydrophilic moiety would be subsequently shed by the intratumoral GSH after cellular internalization and result in the agglomeration of nanocarriers inside tumor cells, consequently impeding the nanoparticle exocytosis to enhance their intracellular retention. The enhanced retention could elevate the intracellular EP level and effectively boost the tumor cell killing effect. In addition to the therapeutic benefits, the Fe 3 O 4 nanocage could also be used for the magnetic resonance imaging of the tumor area. The assorted benefits of the composite nanosystem are anticipated to be advantageous for the treatment of drug-resistant hypoxic tumors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this work, a tumor microenvironment (TME)-responsive biodegradable MnSiO 3 @Fe 3 O 4 nanoplatform for dual-mode magnetic resonance imaging (MRI)-guided combinatorial cancer therapy was constructed. Fe 3 O 4 nanoparticles decorated on the surface of MnSiO 3 could effectively obstruct the pores of MnSiO 3 and reduce the leakage of anticancer drugs under physiological conditions. The structure of the nanoplatform was broken under the weakly acidic and high-concentration glutathione conditions in the TME, resulting in the separation of the Fe 3 O 4 nanoparticles from the nanoplatform and rapid drug release. In addition, the exfoliated Fe 3 O 4 and released Mn 2+ can help reduce the interference between their T 1 and T 2 contrast abilities, resulting in dual-mode MRI contrast enhancement. Furthermore, during the exfoliation process of the Fe 3 O 4 nanocrystals, the catalytic activity of the Fe 3 O 4 nanocrystals toward a Fenton-like reaction within cancer cells could be improved because of the increase in specific surface area, which led to the generation of highly toxic hydroxyl radicals and induced HeLa cell apoptosis. The nanoplatform also displayed excellent T 1 -T 2 dual-mode MRI contrast enhancement and anticancer activity in vivo with reduced systemic toxicity. Thus, this multifunctional nanoplatform could be a potential nanotheranostic for dual-mode MRI-guided combinatorial cancer therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A promising theranostic nanosystem VK3-CPT@Ru-CD is designed and fabricated by the host-guest driven self-assembly between the fluorescent adamantine-functionalized Ru(II) complexes and the ROS-labile-cyclodextrin modified thioketal linkers, in which anticancer drug camptothecin (CPT) and vitamin K3 (VK3) are effectively co-encapsulated. On account of the generative feedback between the intracellular redox cycling of VK3 and the high degree of ROS-triggered collapse of nanoparticles, VK3-CPT@Ru-CD can facilitate cancer-specific ROS amplification and drug release selectively in cancer cells, thus realizing the selective killing of tumor with minimal side-effects both in vitro and in vivo, the therapeutic effect of which is more prominent than the free anti-cancer drugs. More interestingly, the menadione structure of encapsulated VK3 can effectively quench the inherent fluorescence of Ru-CD, and a fluorescence lightening up phenomenon is observed accompanied with the ROS-triggered drug release, which can be utilized for real-time tracking of drug release in vitro and in vivo., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

At the intersection of the newly emerging fields of optoacoustic imaging and theranostic nanomedicine, promising clinical progress can be made in dismal prognosis of ovarian cancer. An acidic pH targeted wormhole mesoporous silica nanoparticle (V7-RUBY) was developed to serve as a novel tumor specific theranostic nanoparticle detectable using multispectral optoacoustic tomographic (MSOT) imaging. We report the synthesis of a small, < 40 nm, biocompatible asymmetric wormhole pore mesoporous silica core particle that has both large loading capacity and favorable release kinetics combined with tumor-specific targeting and gatekeeping. V7-RUBY exploits the acidic tumor microenvironment for tumor-specific targeting and tumor-specific release. In vitro, treatment with V7-RUBY containing either paclitaxel or carboplatin resulted in increased cell death at pH 6.6 in comparison to drug alone (p < 0.0001). In orthotopic ovarian xenograft mouse models, V7-RUBY containing IR780 was specifically detected within the tumor 7X and 4X higher than the liver and >10X higher than in the kidney using both multispectral optoacoustic tomography (MSOT) imaging with secondary confirmation using near infrared fluorescence imaging (p < 0.0004). The V7-RUBY system carrying a cargo of either contrast agent or an anti-neoplastic drug has the potential to become a theranostic nanoparticle which can improve both diagnosis and treatment of ovarian cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Real-time monitoring drug-release is often regarded crucial in theranostics nanomedicine design, since it provides precise establishment of spatio-temporal activation of the drug-release in vitro and in vivo. A symmetrical self-immolative drug-dye conjugation (DDC) prodrug is developed in this study with disulfide bond as the trigger. The prodrug can be escorted by targeting PEG-PLGA micelles and hereby accumulated in the tumor by both active and passive targeting effect. Glutathione (GSH) with higher concentration in the tumor microenvironment can readily cleave the disulfide bond to initiate a subsequent decomposition of DDC, where the drug and dye can be released simultaneously in a strict one-to-one mode. Upon the disintegration, the "Turned-On" probe can emit near-infrared (NIR) fluorescence, with the aim of providing accurate and real-time information for the prodrugs' activation and biodistribution in vivo in a non-invasive way. Furthermore, the released dye can meanwhile act as a photothermic sensitizer, which can in-situ assist a deep penetration for the released drug in the tumor tissue with enhanced therapeutic efficiency. This "babysitting" strategy provides new reference for designing versatile theranostic nanomedicines for preclinical evaluations and an alternative approach for hyperthermia perfusion in clinic., (Copyright © 2018. Published by Elsevier Ltd.)

Radiolabeled nanomaterials, especially those with ultra-small structures, have been the research focus in recent years, and thus may open up new prospects for clinical diseases theranostics. Herein, fluorinated Pd nanosheets labeled with Gd or radionuclides are developed as multimodal platforms for tumor theranostics. These nanomaterials decorated by functional polyethylene glycol demonstrate ultrahigh 19 F MRI signal, ultrasmall size and good dispersibility. These ultrasmall materials exhibit good biocompatibility and easily to be modified for multimodal imaging (SPECT/MRI/PAI) by assembling the functional groups like building blocks. Furthermore, with high accumulation in tumor sites, under the guidance of multimodal imaging, combined photothermal therapy and radiotherapy are performed and synergistic effects are obtained. By comparing the in vivo behaviors of nanostructures labeled by different nuclides, the present study suggests the pH-sensitive radioiodinated Pd nanosheet which has unexpected T/NT ratio (>4-fold tumor-to-muscle ratio) in SPECT imaging and solves the critical high background issue of nanoprobes, could improve diagnostic accuracy and guide combination therapy. In summary, this functionalized nanoplatform with promising imaging and therapeutic efficacy has great potential for precision theranostic nanomedicines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pretargeted nuclear imaging and radiotherapy have recently attracted increasing attention for diagnosis and treatment of cancer with nanomedicines. This is because it conceptually offers better imaging contrast and therapeutic efficiency while reducing the dose to radiosensitive tissues compared to conventional strategies. In conventional imaging and radiotherapy, a directly radiolabeled nano-sized vector is administered and allowed to accumulate in the tumor, typically on a timescale of several days. In contrast, pretargeting is based on a two-step approach. First, a tumor-accumulating vector carrying a tag is administered followed by injection of a fast clearing radiolabeled agent that rapidly recognizes the tag of the tumor-bound vector in vivo. Therefore, pretargeting circumvents the use of long-lived radionuclides that is a necessity for sufficient tumor accumulation and target-to-background ratios using conventional approaches. In this review, we give an overview of recent advances in pretargeted imaging strategies. We will critically reflect on the advantages and disadvantages of current state-of-the-art conventional imaging approaches and compare them to pretargeted strategies. We will discuss the pretargeted imaging concept and the involved chemistry. Finally, we will discuss the steps forward in respect to clinical translation, and how pretargeted strategies could be applied to improve state-of-the-art radiotherapeutic approaches., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the relationship between polymer chemical structure and its performance of photoacoustic imaging (PAI) and photothermal therapy (PTT) is important for developing ideal PAI/PTT agents. In this report, four semiconducting polymer nanoparticles (SPNs) with different donor-acceptor architectures are self-assembled for highly effective PAI-guided PTT. In particular, SPN1 with the longest π-conjugation length and the highest mass extinction coefficient which are beneficial for intramolecular charge transfer as well as light harvesting, exhibits the highest photothermal conversion efficiency up to 52.6%. Moreover, the as-prepared SPN1 possess good water-dispersibility, robust size-stability and excellent photothermal properties. Furthermore, the SPN1 not only exhibits a remarkable cancer cell-killing ability but also shows a prominent tumor inhibition capacity. Finally, the as-prepared water-dispersible SPN1 displays good biocompatibility and biosafety, making it a promising candidate for future biomedical applications. Considering the plenty of near-infrared absorbing semiconducting polymer available, our work provides fundamental insights for rational design and preparation of highly efficient SPN-based PAI/PTT agents for cancer theranostics., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Co-delivery of two drugs with diverse physicochemical properties and specific administration order for cancer theranostics are vitally important for drug resistance conquering and side effects reducing. Consequently, we explored a unique amphiphilic PCL-AuNC/Fe(OH) 3 -PAA Janus nanoparticle (JNP) to simultaneously preserve the hydrophilic drug (doxorubicin) and hydrophobic drug (docetaxel) in their distinct domains. Owing to their extraordinary heterostructure and independent pH and NIR sensitive properties, the optional sequential drug release by a single inorganic JNP was realized for the first time, and the results presented the synchronous release of two drugs had 5% better therapeutic effect. In addition, the excellent computed X-ray tomography/magnetic resonance (CT/MR) imaging capabilities from AuNC and Fe(OH) 3 suggested our JNPs could effectively guide the cancer therapy. Furthermore, the mice treated with dual drug loaded PCL-AuNC/Fe(OH) 3 -PAA JNPs under near infrared (NIR) laser irradiation showed better tumor inhibition than solo drug, cocktail and dual drug treated groups, indicating the effectivity and significance of combined cancer therapy., (Copyright © 2018. Published by Elsevier Ltd.)

Low selectivity is a major problem for cancer theranostics that has promoted the development of molecularly-responsive nanomaterials. Herein, we report a novel doxorubicin (DOX)-loaded degradable cobalt oxide nanoprism (Co 3 O 4 -DOX) for T 1 /T 2 ratiometric magnetic resonance imaging (MRI)-monitored synergistic cancer therapy that simultaneously responds to intratumoral oxidability and acidity. Co 3 O 4 -DOX degraded under both H 2 O 2 -rich and acidic conditions, producing Co 3+ and releasing DOX, not only resulted in an MRI contrast switch from T 2 to T 1 , but also led to DOX luminescence recovery by weakening energy transfer. Thus, highly sensitive and selective H 2 O 2 detection was achieved by these changes in MRI and luminescence signals. Importantly, Co 3 O 4 -DOX showed outstanding T 1 /T 2 ratiometric MRI performance in vivo, significantly improving the contrast between tumor and normal tissues. Moreover, the produced Co 3+ also resulted in intracellular radical generation for chemodynamic therapy, which had a synergistic effect with the photothermal and chemotherapy induced by Co 3 O 4 and DOX, respectively. Under ratiometric MRI guidance, successful synergistic cancer therapy was performed on a tumor-bearing mice model. This work provides a new imaging application to improve selectivity that uses molecularly-responsive magnetic nanomaterials for ratiometric MRI tumor imaging and cancer theranostics., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Treating the hypoxic region of the tumor remains a significant challenge. The goals of this study are to develop an exosome platform that can target regions of tumor hypoxia and that can be monitored in vivo using magnetic particle imaging (MPI). Four types of exosomes (generated under hypoxic or normoxic conditions, and with or without exposure to X-ray radiation) were isolated from MDA-MB-231 human breast cancer cells. Exosomes were labeled by DiO, a fluorescent lipophilic tracer, to quantify their uptake by hypoxic cancer cells. Subsequently, the exosomes were modified to carry SPIO (superparamagnetic iron oxide) nanoparticles and Olaparib (PARP inhibitor). FACS and fluorescence microscopy showed that hypoxic cells preferentially take up exosomes released by hypoxic cells, compared with other exosome formulations. In addition, the distribution of SPIO-labeled exosomes was successively imaged in vivo using MPI. Finally, the therapeutic efficacy of Olaparib-loaded exosomes was demonstrated by increased apoptosis and slower tumor growth in vivo. Our novel theranostic platform could be used as an effective strategy to monitor exosomes in vivo and deliver therapeutics to hypoxic tumors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Non-invasive imaging-guided tumor therapy requires new-generation bio-nanomaterials to sensitively respond to the unique tumor microenvironment for precise diagnosis and efficient treatment. Here, we report such a theranostic nanoplatform by engineering defect-rich multifunctional Cu-doped layered double hydroxide (Cu-LDH) nanoparticles, which integrates pH-sensitive T 1 -magnetic resonance imaging (MRI), acid-enhanced photothermal therapy and heat-facilitated chemotherapy. As characterized with EXAFS and XPS, smaller Cu-LDH nanoparticles possess a considerable amount of defects around Cu cations, an advantageous microstructure that enables a high photothermal conversion of 808 nm NIR laser (53.1%). The exposure of CuOH octahedra on the LDH surface makes the photothermal conversion significantly acid-enhanced (53.1% at pH 7.0 vs. 81.9% at pH 5.0). This Cu peculiar microstructure also makes T 1 -MRI very pH-sensitive, a desirable guide for subsequent tumor photothermal therapy. Combined photothermal therapy and chemotherapy lead to nearly complete elimination of tumor tissues in vivo with a low injection dose of agents. Therefore, this novel defect-rich Cu-LDH nanoplatform is one of promising tumor-specific nanotheranostic agents for non-invasive imaging-guided combinational therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Interest in theranostic agents has continued to grow because of their promise for simultaneous cancer detection and therapy. A platform-based nanosized combination agent suitable for the enhanced diagnosis and treatment of cancer was prepared using polymeric polyethylene glycol-phosphatidylethanolamine-based micelles loaded with both, poorly soluble chemotherapeutic agent paclitaxel and hydrophobic superparamagnetic iron oxide nanoparticles (SPION), a Magnetic Resonance Imaging contrast agent. The co-loaded paclitaxel and SPION did not affect each other's functional properties in vitro. In vivo, the resulting paclitaxel-SPION-co-loaded PEG-PE micelles retained their Magnetic Resonance contrast properties and apoptotic activity in breast and melanoma tumor mouse models. Such theranostic systems are likely to play a significant role in the combined diagnosis and therapy that leads to a more personalized and effective form of treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Herein, poly(pyrrole-3-carboxylic acid) (PPyCOOH) nanoneedles with abundant carboxyl groups were synthesized by aqueous dispersion polymerization method using pyrrole-3-carboxylic acid as conductive polymer monomer. The PPyCOOH nanoneedles not only owned good photothermal performance, but also more importantly showed enhanced tumor cell uptake efficiency (1.64 fold) compared with size and zeta-potential matched nanospheres. After loading photosensitizer aluminum phthalocyanine tetrasulfonate (AlPCS 4 ) and modifying with poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) onto the PPyCOOH nanoneedles, novel nanoneedle complexes (AlPCS 4 @PPyCONH-PAH-PAA) integrating photodynamic therapy (PDT) and photothermal therapy (PTT) were successfully fabricated. The as-prepared nanoneedle complexes improved uptake efficiency of AlPCS 4 both in vitro and in vivo. Moreover, the nanoneedle complexes have infrared thermal and fluorescent properties. By combined PDT/PTT under the guiding of dual modal imaging, the tumors in mice were completely eliminated and no recurrence was observed in 30 days after treatment, indicating that PPyCOOH nanoneedles have great potential as a novel drug carrier for constructing multifunctional nanoplatform used for cancer treatment., (Copyright © 2018. Published by Elsevier Ltd.)

Recently, theranostic has drawn tremendous attention by virtue of the nanotechnology development and new material exploration. Herein, we reported a novel theranostic system by loading Au nanoclusters (AuNCs) and Chlorin e6 (photosensitizer, Ce6) onto the monolayer nanosheet surface of Gd-doped layered double hydroxide (Gd-LDH). The as-prepared Ce6&AuNCs/Gd-LDH exhibits a largely enhanced fluorescence quantum yield (QY) of 18.5% relative to pristine AuNCs (QY = 3.1%) as well as superior T 1 magnetic resonance imaging (MRI) performance (r 1  = 17.57 mM -1 s -1 ) compared with commercial MRI contrast agent (Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA): r 1  ≈ 3.4 mM -1 s -1 ), resulting from a synergistic effect between AuNCs and Gd-LDH. In addition, both in vitro and in vivo therapeutic evaluations demonstrate an efficient dual-modality imaging guided anticancer performance, especially the synergetic enhanced magnetic resonance/fluorescence (MR/FL) visualization of tumor site. Therefore, this work demonstrates a successful paradigm for the design and preparation of LDHs monolayer-based theranostic material, which holds great promises in practical applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC). Necroptotic tumor cells can release danger associated molecule patterns (DAMPs) like heat shock proteins, being more immunogenic than naïve tumor cells. Here, nano-size "artificial necroptotic cancer cell" (αHSP70p-CM-CaP) composing of phospholipid bilayer and a phosphate calcium core was designed as a flexible vaccine platform for co-delivering cancer membrane proteins (CM), DAMPs signal-augmenting element α-helix HSP70 functional peptide (αHSP70p) and CpG to both natural killer (NK) cells and APC. Mechanically, immunogenic B16OVA tumor cells membrane-associated antigens and αHSP70p were reconstituted in artificial outer phospholipid bilayer membrane via one-step hydration and CpG encapsulated in the phosphate calcium core. The resulted αHSP70p-CM-CaP exhibited 30 nm in diameter with the immunogenic membrane proteins reserved in the particles to produce synergistic effect on bone marrow derived dendritic cells maturation and antigen-presentation. Following αHSP70p-CM-CaP vaccination, efficient lymph node trafficking and multi-epitope-T cells response was observed in mice. Vitally, αHSP70p-CM-CaP was also able to induce expansion of IFN-γ-expressing CD8 + T cells and NKG2D + NK cells subsets. Most promisingly, αHSP70p-CM-CaP vaccination led to the killing of target cells and tumor regression in vivo when combined with anti-PD-1 antibody treatment on mice B16OVA melanoma models. Altogether, we demonstrated proof-of-concept evidence for the feasibility, capability and safety of a nanovaccine platform towards efficient personalized anticancer application., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Theranostic agents with perfect properties are needed urgently for the development of imaging guided photothermal therapy (PTT). In this work, Gd-integrated polypyrrole nanotheranostic agent (PPy@BSA-Gd) was successfully built through selecting bovine serum albumin (BSA) as both stabilizers for polymerization and biomimetic mineralization in "one pot". The obtained PPy@BSA-Gd possessed high stability and excellent photothermal property. Besides, relevant cellular assays indicated that PPy@BSA-Gd had fantastic cytocompatibility which could be further internalized by cancer cells. Due to their high longitudinal relaxivity value (r 1  = 10.203 mM -1  s -1 ), PPy@BSA-Gd could serve as considerable probe for T 1 -weighted magnetic resonance imaging (MRI). After tail vein injection of PPy@BSA-Gd, the MR signal of tumor section exhibited a time-dependent increase, indicating effective tumor accumulation of PPy@BSA-Gd. Notably, when exposed to 808 nm laser, the tumor growth of PPy@BSA-Gd treated mice could be inhibited by photothermal ablation successfully. All the results demonstrated the well-designed PPy@BSA-Gd have the potential for tumor diagnose and photothermal therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Bismuth (Bi)-based semiconductors and composites have been well developed for cancer treatments due to their multimodal diagnostic and therapeutic functions, while the development of metallic Bi nanocrystals is rather hindered by the easy-oxidation and unsatisfactory near-infrared photoabsorption. Herein, we prepared uniform Bi nanoparticles (∼40 nm) capped with thiol ligands (Bi-SR) through the chemical reduction method and then surface-modified them with PEGylated phospholipids. The resulting Bi-SR-PEG has strong NIR absorbance and high photothermal conversion efficiency of 45.3%. Importantly, thiol ligands on the surface of Bi-SR-PEG can significantly prevent the metal Bi core from oxidation because of the strong chemisorption energy between sulfur and metal, thus maintaining the high stability and long-term near-infrared photoabsorption. More importantly, given the low toxicity, good blood compatibility and high X-ray attenuation coefficient, Bi-SR-PEG can passively accumulatein the tumor area through intravenous injection, endowing them with the simultaneous tumor CT imaging and thermoradiotherapy, and thereafter they can be metabolized and excreted from the mice body overtime. Therefore, the satisfying therapeutic effect of tumors can be achieved, undoubtedly verifying that Bi-SR-PEG can be used as a novel, stable and all-in-one type theranostic nanoagent for cancer treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The applications of inorganic theranostic agents in clinical trials are generally limited to their innate non-biodegradability and potential long-term biotoxicity. To address this problem, herein via a straightforward and tailored space-confined on-substrate route, we obtained rhenium trioxide (ReO 3 ) nanocubes (NCs) that display a good biocompatibility and biosafety. Importantly, their aqueous dispersion has high localized surface plasmon resonance (LSPR) absorbance in near-infrared (NIR) region different from previous report, which possibly associates with the charge transfer and structural distortion in hydrogen rhenium bronze (H x ReO 3 ), as well as ReO 3 's cubic shape. Such a high LSPR absorbance in the NIR region endows them with photoacoustic (PA)/infrared (IR) thermal imaging, and high photothermal conversion efficiency (∼57.0%) for efficient ablation of cancer cells. Also, ReO 3 NCs show X-ray computed tomography (CT) imaging derived from the high-Z element Re. More attractively, those ReO 3 NCs, with pH-dependent oxidized degradation behaviors, are revealed to be relatively stable in hypoxic and weakly acidic microenvironment of tumor for imaging and treatment whilst degradable in normal physiological environments of organs to enable effective clearance. In spite of their degradability, ReO 3 NCs still possess tumor targeting capabilities. We thus develop a simple but powerful, safe and biodegradable inorganic theranostic platform to achieve PA/CT/IR imaging-guided cancer photothermal therapy (PTT) for improved therapeutic efficacy and decreased toxic side effects., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The high incidence of colorectal cancer worldwide is currently a major health concern. Although conventional chemotherapy and surgery are effective to some extent, there is always a risk of relapse due to associated side effects, including post-surgical complications and non-discrimination between cancer and normal cells. In this study, we developed a small molecule-based theranostic system, Gal-Dox, which is preferentially taken up by colon cancer cells through receptor-mediated endocytosis. After cancer-specific activation, the active drug Dox (doxorubicin) is released with a fluorescence turn-on response, allowing both drug localization and site of action to be monitored. The therapeutic potency of Gal-Dox was also evaluated, both in vivo and ex vivo, thus illustrating the potential of Gal-Dox as a colorectal cancer theranostic with great specificity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this report, a biomimetic theranostic oxygen (O 2 )-meter (cancer cell membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was constructed for cancer targeted and phosphorescence image-guided photodynamic therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable self-quenching behaviors for favorable biological O 2 sensing and PDT. Besides, endowed by the surface functionalization of cancer cell membrane, the homotypic targeting and immune escape abilities of mPPt could dramatically enhance its cancer targeting ability. Importantly, the O 2 -dependent phosphorescence responsibility of mPPt could be employed to pre-evaluate the real time O 2 level in situ and guide the PDT under light irradiation. A significant anticancer effect is observed after intravenous injection of mPPt and subsequent treatment with PDT with no obvious side effects. As a versatile platform for cell imaging, O 2 fluctuation monitoring as well as PDT, this biomimetic O 2 -meter exhibits great potential for biological analysis and personalized cancer theranostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease. Combined with high-throughput characteristics, the employment of organ-on-chip technology would allow pharmaceutical companies and clinicians to test new therapeutic compounds and therapies. This will permit the screening of a large battery of new drugs in a fast and economic manner, to accelerate the diagnosis of the disease in the near future, and to test personalized treatments using cells from patients. In this review, we describe the latest advances in the field of organ-on-chip models of cancer metastasis and their integration with advanced imaging, screening and biosensing technologies for future precision medicine applications. We focus on their clinical applicability and market opportunities to drive us forward to the next generation of tumor models for improved cancer patient theranostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Semiconducting polymers with specific absorption are useful in various applications, including organic optoelectronics, optical imaging, and nanomedicine. However, the optical absorption of a semiconducting polymer with a determined structure is hardly tunable when compared with that of inorganic semiconductors. In this work, we show that the optical absorption of polymer nanoparticles from one conjugated backbone can be effectively tuned through judicious design of the particle morphology and the persistence length of polymers. Highly absorbing near-infrared (NIR) polymers based on diketopyrrolopyrrole-dithiophene (DPP-DT) are synthesized to have different molecular weights (MWs). The DPP-DT polymer with a large molecular weight and high persistence length exhibited remarkably high optical absorption with a peak mass extinction coefficient of 81.7 L g -1  cm -1 , which is one of the highest value among various photothermal agents reported to date. Particularly, the polymer nanoparticles with different sizes exhibit broadly tunable NIR absorption peaks from 630 to 811 nm. The PEGylated small polymer dots (Pdots) show good NIR light-harvesting efficiency and high non-radiative decay rates, resulting in a relatively high photothermal conversion efficiency in excess of 50%. Thus, this Pdot-based platform can serve as promising photothermal agents and photoacoustic probes for cancer theranostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bacterial infection has been a threat to human health, and so early diagnosis and treatment of bacterial infection is an urgent problem that needs to be solved. In this work, a multifunctional theranostic selenium nanoplatform (Se@PEP-Ru NPs) with early imaging diagnosis and efficient treatment of bacterial infections was designed and constructed. First, the antibacterial peptide UBI29-41 (PEP) was linked to functionalized Selenium nanoparticles (NPs), which enhanced the stability of the antimicrobial peptide and also caused the nanocomposites to specifically target bacterial infection. Ruthenium complexes with good antibacterial activity and fluorescence properties were then coated on to their outer layers. It was worth mentioning that, when the resulting nanoprobe was injected into mice by intravenous injection it was found to be sensitive to sites of bacterial infection for selective fluorescence imaging and targeted therapy. Thus, it can be used to distinguish between bacterial infection, inflammation, and tumor-induced tissue infection with high specificity. In the further antibacterial activity experiments, Ruthenium complexes showed synergistic antimicrobial activity with Se NPs, which indicated that the antibacterial activity of Se@PEP-Ru NPs was the strongest that could promote wound healing. Thus, Se@PEP-Ru NPs appears to be a promising antimicrobial with good biocompatibility, excellent selectivity, and potent antimicrobial activity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Overcoming biological barriers to imaging-guided site-specific delivery of therapeutics is the goal of current nanomedicine designs. Here, multifunctional polymer-coated carbon nanodots with an interleukin-6 (IL-6) fragment peptide for receptor-targeting (pCDPI) were prepared for drug delivery. The pCDPI exhibits small hydrodynamic diameters, high water solubility and biocompatibility. In vitro and in vivo results demonstrated that pCDPI can overcome the blood-brain barrier (BBB) and deeply penetrate into orthotopic glioma in mice, to inhibit IL-6-induced cell proliferation and achieve imaging-guided targeted drug delivery. Simultaneously, a pH-sensitive sustained release of doxorubicin (DOX) accompanied with real-time fluorescence monitoring was realized. A distinct synergistic therapeutic outcome could be achieved which suggests the presented nanomedicine having promising potential for future cancer treatments., (Copyright © 2017. Published by Elsevier Ltd.)

Biocompatible single-component theranostic agents integrating multimodal imaging and therapeutic functions (namely, "all-in one" agents) are highly desired for clinical cancer treatments. Herein, PEGylated pure metallic bismuth nanocrystals (Bi-PEG NCs) have been developed to be a competent theranostic agent for in vivo high-performance multimodal bio-imaging and photothermal ablation of tumors. The resultant Bi-PEG NCs show excellent physiological stability, biocompatibility, prolonged blood circulation half-life and preferential tumor accumulation. Thanking to the strong near-infrared (NIR) absorbance as well as the high photothermal conversion efficiency and conversion stability, highly effective in vivo photothermal ablation on tumors has been realized upon NIR irradiation, without noticeable toxicity. Impressively, the Bi-PEG NCs show ultrahigh X-ray computed topography (CT) enhancement efficiency (∼60.3 HU mL mg -1 ), overwhelming all CT contrast agents reported so far. Combining the strong CT contrast ability and photoacoustic/photothermal effect, high-contrast CT, photoacoustic (PA) and infrared thermal (IRT) triple-modal imaging have been demonstrated both in vitro and in vivo. This work highlights the potentials of such NCs as a powerful "all-in-one" theranostic nanoplatform for bioimaging and antitumor therapy, and may have provided a rather promising candidate for clinically-applied antitumor treatments based on single-component agents., (Copyright © 2017. Published by Elsevier Ltd.)

The clinical ultrasound (US)-based theranostic biomedicine suffers from the critical issue that traditional microbubbles (MBs) have lots of drawbacks such as low stability, large particle size, difficult structural control, etc. The unique composition, structure and functionality of inorganic micro/nanoplatforms have shown their great prospect for solving these critical issues and drawbacks of traditional organic MBs. This review summarizes and discusses the state-of-art development on exploring inorganic micro/nanoparticles for versatile US-based biomedical applications, ranging from US imaging, photoacoustic imaging, sonodynamic therapy, high intensity-focused US ablation and US-triggered chemotherapy. These inorganic micro/nanoplatforms include silica-based particles, Au, carbon nanotubes, TiO 2 , manganese oxide, iron oxide, Prussian blue, inorganic gas-generating nanoparticles and their versatile composite micro/nanosystems. Especially, their unique structure/composition-functionality relationships and biocompatibility/biosafety in US-based theranostics have been discussed and revealed in detail. Their facing challenges and future developments are finally discussed to promote their further clinical translations. It is highly expected that these inorganic micro/nanoplatforms will enter the clinical stage to benefit the personalized theranostics biomedicine based on their unique functionalities and high performance as necessarily required in US-based theranostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The therapeutic potential of hyperbranched polymers targeted to prostate cancer and loaded with doxorubicin was investigated. Polyethylene glycol hyperbranched polymers were synthesised via RAFT polymerisation to feature glutamate urea targeting ligands for PSMA on the periphery. The chemotherapeutic, doxorubicin, was attached to the hyperbranched polymers through hydrazone formation, which allowed controlled release of the drug from the polymers in vitro endosomal conditions, with 90% release of the drug over 36 h. The polymers were able to target to PSMA-expressing prostate cancer cells in vitro, and demonstrated comparable cytotoxicity to free doxorubicin. The ability of the hyperbranched polymers to specifically facilitate transport of loaded doxorubicin into the cells was confirmed using live cell confocal imaging, which demonstrated that the drug was able to travel with the polymer into cells by receptor mediated internalisation, and subsequently be released into the nucleus following hydrazone degradation. Finally, the ability of the complex to induce a therapeutic effect on prostate cancer cells was investigated through a long term tumour regression study, which confirmed that the DOX-loaded polymers were able to significantly reduce the volume of subcutaneous prostate tumours in vivo in comparison to free doxorubicin and a polymer control, with no adverse toxicity to the animals. This work therefore demonstrates the potential of a hyperbranched polymer system to be utilised for prostate cancer theranostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In vivo monitoring of the biodistribution and activation of prodrugs is highly attractive, and the self-immolative dendritic architecture is deemed as a promising approach for constructing theranostic prodrug in which the release/activation of different payloads is needed. Herein, A GSH-triggered and self-immolative dendritic platform comprising an anticancer drug camptothecin (CPT), a cleavable linker and a two-photon NIR fluorophore (dicyanomethylene-4H-pyran, DCM) has been developed for in situ tracking of drug release and antitumour therapy. In vitro experiments demonstrate that, the presence of glutathione (GSH) induces the cleavage of the self-immolative linker, resulting in comitant release of the drug and the dye. Upon cell internalization and under one- or two-photon excitation, prominent intracellular fluorescence can be observed, indicating the release of the payloads in live cells. Upon loaded in phospholipid vesicles, the prodrug has also been successfully utilized for in vivo and in situ tracking of drug release and cancer therapy in a mouse model. Several hours post injection, the prodrug generates strong fluorescence on tumour sites, demonstrating the prodrug's capability of monitoring the on-site drug release. Moreover, the prodrug shows considerable high activity and exerts obvious inhibition towards tumour growth. This work suggests that the prodrug with self-immolative dendritic structure can work well in vivo and this strategy may provide an alternative approach for designing theranostic drug delivery systems., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The discovery of adult neurogenesis drastically changed the therapeutic approaches of central nervous system regenerative medicine. The stimulation of this physiologic process can increase memory and motor performances in patients affected by neurodegenerative diseases. Neural stem cells contribute to the neurogenesis process through their differentiation into specialized neuronal cells. In this review, we describe the most important methods developed to restore neurological functions via neural stem cell differentiation. In particular, we focused on the role of nanomedicine. The application of nanostructured scaffolds, nanoparticulate drug delivery systems, and nanotechnology-based real-time imaging has significantly improved the safety and the efficacy of neural stem cell-based treatments. This review provides a comprehensive background on the contribution of nanomedicine to the modulation of neurogenesis via neural stem cell differentiation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Gold nanoparticles hold great promise as anti-cancer theranostic agents against cancer by actively targeting the tumor cells. As this potential has been supported numerously during in vitro experiments, the effective application is hampered by our limited understanding and control of the interactions within complex in vivo biological systems. When these nanoparticles are exposed to a biological environment, their surfaces become covered with proteins and biomolecules, referred to as the protein corona, reducing the active targeting capabilities. We demonstrate a chemical strategy to overcome this issue by reducing the protein corona's thickness by blocking the active groups of the self-assembled monolayer on gold nanostars. An optimal blocking agent, 2-mercapto ethanol, has been selected based on charge and length of the carbon chain. By using a nanobody as a biological ligand of the human epidermal growth factor 2 receptor (HER2), the active targeting is demonstrated in vitro and in vivo in an experimental tumor model by using darkfield microscopy and photoacoustic imaging. In this study, we have established gold nanostars as a conceivable theranostic agent with a specificity for HER2-positive tumors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)