The emergence of drug-resistant bacteria and easy recurrence has been challenging in the clinical treatment of skin abscesses resulting from bacterial infections (e.g., by Staphylococcus aureus (S. aureus)). Herein, an antibacterial nanoagent capable of modulating the abscess microenvironment is designed to enhance photodynamic treatment of skin abscesses, and subsequently activate the immune system to effectively prevent abscess recurrence. In the system, manganese dioxide nanoparticles (MnO2 NPs) with high catalytic reactivity toward H2 O2 are modified with photosensitizer chlorine e6 (Ce6) and coated with polyethylene glycol (PEG). The obtained Ce6@MnO2 -PEG NPs, by triggering the decomposition of lesion endogenous H2 O2 , are able to effectively relieve the hypoxic abscess microenvironment during S. aureus infection. The light-triggered photodynamic bacterial killing effect could thus be remarkably enhanced, resulting in effective in vivo therapy of S. aureus-induced skin abscesses. Interestingly, a notable pathogen-specific immunological memory effect against future infection by the same species of bacteria is elicited after such treatment, owing to the release of bacterial antigens post photodynamic therapy (PDT) together with the adjuvant-like function of manganese ions to activate the host immune system. This work thus presents a new type of photodynamic nanoagent particularly promising for highly effective light-triggered abscess treatment and prevention of abscess recurrence.

The development of activatable nanoplatforms to simultaneously improve diagnostic and therapeutic performances while reducing side effects is highly attractive for precision cancer medicine. Herein, we develop a one-pot, dopamine-mediated biomineralization method using a gas diffusion procedure to prepare calcium carbonate-polydopamine (CaCO3-PDA) composite hollow nanoparticles as a multifunctional theranostic nanoplatform. Because of the high sensitivity of such nanoparticles to pH, with rapid degradation under a slightly acidic environment, the photoactivity of the loaded photosensitizer, i.e., chlorin e6 (Ce6), which is quenched by PDA, is therefore increased within the tumor under reduced pH, showing recovered fluorescence and enhanced singlet oxygen generation. In addition, due to the strong affinity between metal ions and PDA, our nanoparticles can bind with various types of metal ions, conferring them with multimodal imaging capability. By utilizing pH-responsive multifunctional nanocarriers, effective in vivo antitumor photodynamic therapy (PDT) can be realized under the precise guidance of multimodal imaging. Interestingly, at normal physiological pH, our nanoparticles are quenched and show much lower phototoxicity to normal tissues, thus effectively reducing skin damage during PDT. Therefore, our work presents a unique type of biomineralized theranostic nanoparticles with inherent biocompatibility, multimodal imaging functionality, high antitumor PDT efficacy, and reduced skin phototoxicity.

Tumor hypoxia is known to be one of critical factors that aggravate the tumor resistance to photodynamic therapy (PDT) in which oxygen is essential for tumor destruction. Herein, catalase, an enzyme to trigger hydrogen peroxide (H2O2) decomposition, is modified by in-situ free radical polymerization, using meso-tetra(p-hydroxyphenyl) porphine (THPP) as the cross-linker to enable condensed grafting of short polyethylene glycol (PEG) chains on the protein surface as a permeable brush-like safeguard. The formulated catalase-entrapped nanocapsules (CAT-THPP-PEG) with enhanced enzyme stability can be labeled with 99mTc4+, a radioisotope ion that is chelated by the porphyrin structure of THPP, to allow in vivo single-photon emission computed tomography (SPECT) imaging. It is found that such CAT-THPP-PEG nanoparticles exhibit efficient tumor passive retention after intravenous injection, and are able to greatly relieve tumor hypoxia by triggering the decomposition of tumor endogenous H2O2 into oxygen. With THPP functioning as a photosensitizer, in vivo PDT is further conducted, achieving a remarkable antitumor therapeutic effect. This work presents an enzyme modification strategy by in-situ polymerization with photosensitizer as the cross-linker to develop multifunctional nano-theranostics with strengthened enzymatic stability, efficient tumor passive homing, SPECT imaging capability, enhanced PDT efficacy as well as decreased immunogenicity, promising for clinical translation.

Recently, covalent-organic polymers (COPs), which covalently cross-link different types of organic molecules to form organic network structures, have received significant attention in various fields. However, the design of COPs that allows them to act as therapeutic agents remains to be explored. In the present study, a new class of COPs was fabricated by cross-linking the photosensitizer meso-tetra(p-hydroxyphenyl) porphine (THPP) to a chemotherapeutic pro-drug, cis-platinum (IV); the latter also acts as a reduction-responsive linker. After further conjugation with polyethylene glycol (PEG) in this one-pot reaction, we obtained THPP-Pt-PEG COPs, which can be stored in a lyophilized form and occur as stable nanoparticles in aqueous solution. The THPP-Pt-PEG COPs are effective in killing cancer cells through photodynamic treatment, and exhibited reduction-responsive degradation/drug release behaviors. Upon intravenous injection, the COPs, with a long blood circulation time, showed efficient tumor accumulation. Interestingly, we revealed that after injection of THPP-Pt-PEG COPs, tumors on mice exhibited greatly improved vascular perfusion and largely relieved tumor hypoxia, which favored subsequent photodynamic treatment. Hence, the combined chemo-photodynamic therapy of the COPs offers a remarkably improved therapeutic outcome compared to that with mono-therapies. This work presents a COP-based nanomedicine with high drug loading, lyophilizable formulation, prolonged blood half-life, efficient tumor passive homing, inherent biodegradability, and multiple therapeutic functions to achieve enhanced cancer combination therapy, with promise for clinical translation.

Covalent organic polymers (COPs) are a promising class of cross-linked polymeric networks and porous structures composed of covalent organic molecules that attract extensive attention. Despite increasing interest in applying COPs for applications in nanomedicine, the pH-sensitive COPs that are able to sensitively respond to the slightly acidic tumor microenvironment for tumor-specific drug delivery and therapy remain to be explored to our best knowledge. Herein, a new style of pH-responsive COPs were prepared using acryloyl meso-tetra( p-hydroxyphenyl) porphine (acryloyl-THPP) to react with 4,4'-trimethylene dipiperidine to form the pH-responsive cross-linked biodegradable β-amino esters (BAEs). Amine-modified poly(ethylene glycol) (PEG) was then introduced to terminate the reaction and form the PEG shell. The formulated pH-responsive THPP-BAE-PEG COPs can be utilized to encapsulate anticancer drug doxorubicin (DOX) due to their porous structure. Upon intravenous injection, such DOX-loaded COPs show a prolonged blood circulation as well as an efficient tumor accumulation. Along with the pH-triggered drug release for chemotherapy, the singlet oxygen produced by THPP under light exposure for photodynamic therapy would further endow us a combined treatment strategy, which offers synergistic antitumor effects in our in vivo tumor model experiments. Our study illustrates that COPs fabricated with tumor microenvironment responsive linkers may be a promising type of materials for applications in cancer nanomedicine.

The synthesized MoO2 nanocrystals exhibit excellent photothermal temperature elevation of about 37.5 °C under 808 nm laser irradiation, and tumor inhibition effects with an inhibition rate of up to 80.45% as a photothermal therapy agent against 4T1 cancer cells.

Lymphatic metastasis is the major metastatic pattern of pancreatic cancer and considered as an independent risk factor of survival. However, there is still no effective way for the diagnosis and treatment for lymphatic metastases of pancreatic cancer. In this study, using albumin as a carrier of gemcitabine (Gem), further modified by pyropheophorbide-a, we have designed and synthesized a nanoparticle (NP) compound named "pheophorbide-a (P@)-Gem-human serum albumin (HSA)-NPs". By utilization of its tracer ability of lymphatic metastases, which is triggered by near-infrared irradiation and its visible dying ability, the compound is used for drug delivery tracking, meanwhile as a treating drug, as well as the combined effect of photodynamic therapy and chemotherapy. By the nude mice model of lymphatic metastases of pancreatic cancer (BxPC-3-LN7), we aim to explore the feasibility, effectiveness, and biological safety of diagnosis and treatment for the lymphatic metastases of pancreatic cancer by P@-Gem-HSA-NP, thereby, providing new methods and strategies for the study of nanodrug carrier and research on lymphatic metastases of pancreatic cancer.

Nanoscale coordination polymers (NCPs) self-assembled from metal ions and organic bridging ligands exhibit many unique features promising for applications in nanomedicine. In this work, manganese dioxide (MnO2) nanoparticles stabilized by bovine serum albumin are encapsulated by NCP-shells constructed based on high-Z element hafnium (Hf) ions and c,c,t-(diamminedichlorodisuccinato)Pt(IV) (DSP), a cisplatin prodrug. After further modification with polyethylene glycol (PEG), the formed BM@NCP(DSP)-PEG can simultaneously serve as a radio-sensitizer owing to the strong X-ray attenuation capability of Hf to enhance radiotherapy, as well as a chemotherapeutic agent resulting from the reduction-induced release of cisplatin. Meanwhile, the in situ generated oxygen resulting from MnO2-triggered decomposition of tumor endogenous H2O2 will be greatly helpful for overcoming hypoxia-associated radio-resistance. Upon intravenous injection, BM@NCP(DSP)-PEG shows efficient tumor homing as well as rapid renal excretion, as illustrated by magnetic resonance imaging and confirmed by biodistribution measurement. Notably, an excellent in vivo tumor growth inhibition effect is observed with BM@NCP(DSP)-PEG nanoparticles after the combined chemoradiotherapy treatment. Therefore, the NCP-based composite nanoparticles with inherent biodegradability and no appreciable in vivo toxicity may be a unique type of multifunctional nanoplatform responsive to different parameters in the tumor microenvironment, promising for cancer theranostics with great efficacy.

The development of smart drug delivery systems to realize controlled drug release for highly specific cancer treatment has attracted tremendous attention. Herein, nanoscale coordination polymers (NCPs) constructed from hafnium ions and bis-(alkylthio) alkene (BATA), a singlet-oxygen responsive linker, are fabricated and applied as nanocarriers to realize light-controlled drug release under a rather low optical power density. In this system, NCPs synthesized through a solvothermal method are sequentially loaded with chlorin e6 (Ce6), a photosensitizer, and doxorubicin (DOX), a chemotherapeutic drug, and then coated with lipid bilayer to allow modification with polyethylene glycol (PEG) to acquire excellent colloidal stability. The singlet oxygen produced by such NCP-Ce6-DOX-PEG nanocomposite can be used not only for photodynamic therapy, but also to induce the break of BATA linker and thus the destruction of nanoparticle structures under light exposure, thereby triggering effective drug release. Notably, with efficient tumor accumulation after intravenous injection as revealed by CT imaging, those NCP-Ce6-DOX-PEG nanoparticles could be utilized for combined chemo-photodynamic therapy with great antitumor efficacy. Thus, this work presents a unique type of NCP-based drug delivery system with biodegradability, sensitive responses to light, as well as highly efficient tumor retention for effective cancer combinational treatment.

While immunotherapy has become a highly promising paradigm for cancer treatment in recent years, it has long been recognized that photodynamic therapy (PDT) has the ability to trigger antitumor immune responses. However, conventional PDT triggered by visible light has limited penetration depth, and its generated immune responses may not be robust enough to eliminate tumors. Herein, upconversion nanoparticles (UCNPs) are simultaneously loaded with chlorin e6 (Ce6), a photosensitizer, and imiquimod (R837), a Toll-like-receptor-7 agonist. The obtained multitasking UCNP-Ce6-R837 nanoparticles under near-infrared (NIR) irradiation with enhanced tissue penetration depth would enable effective photodynamic destruction of tumors to generate a pool of tumor-associated antigens, which in the presence of those R837-containing nanoparticles as the adjuvant are able to promote strong antitumor immune responses. More significantly, PDT with UCNP-Ce6-R837 in combination with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade not only shows excellent efficacy in eliminating tumors exposed to the NIR laser but also results in strong antitumor immunities to inhibit the growth of distant tumors left behind after PDT treatment. Furthermore, such a cancer immunotherapy strategy has a long-term immune memory function to protect treated mice from tumor cell rechallenge. This work presents an immune-stimulating UCNP-based PDT strategy in combination with CTLA-4 checkpoint blockade to effectively destroy primary tumors under light exposure, inhibit distant tumors that can hardly be reached by light, and prevent tumor reoccurrence via the immune memory effect.

Metallic oxide nanocrystals with near-infrared plasmon resonance for efficient, stable and biocompatible photothermal cancer therapy Kang Dou, ‡a Wenwen Zhu, ‡b Yousheng Zou, *a Yu Gu, a Jubin Li, a Shengli Zhang, a Zhuang Liu, *b and Haibo Zeng *a a MIIT Key Laboratory of Advanced Display Materials and Devices, Institute of Optoelectronics & Nanomaterials, School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. b Institute of Functional Nano & Soft Materials Laboratory (FUNSOM), Soochow University, Suzhou 215123, China. *Correspondence and requests for material to Yousheng Zou or Haibo Zeng or Zhuang Liu, Email address: yshzou75@njust.edu.cn; zliu@suda.edu.cn; zeng.haibo@njust.edu.cn ‡ These authors contribute to this work equally. †Electronic supplementary information (ESI) available: Synthesis mechanism scheme of MoO2 nanocrystals, Simulation of MoO2 nanocrystals absorption spectrum.

With the rapid development of computer technology, the barriers of communication among different systems caused by system heterogeneity or data structure have been broken down. However, the demands for personalized content for accuracy in resource exchange and delivery are becoming increasingly high. The structures of existing literature resources like papers, patents and books, with different formats and structures, leading to lots of problems in content delivery and inheritance. Thus, based on the XML technology, we design and develop the data exchange system. This system supports the mapping and integration of different structures of literature resource, and parsing resources at the same time, so that users can upload and verify the XML schema files according to their individual demands for data exchange.

Cancer combination therapy to treat tumors with different therapeutic approaches can efficiently improve treatment efficacy and reduce side effects.Herein, we develop a theranostic nano-platform based on polydopamine (PDA) nanoparticles, which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green (ICG), doxorubicin (DOX) and manganese ions (PDA-ICG-PEG/DOX(Mn)), to enable imaging-guided chemo & photothermal cancer therapy.In this system, ICG acts as a photothermal agent, which shows red-shifted near-infrared (NIR) absorbance and enhanced photostability compared with free ICG.DOX, a model chemotherapy drug, is then loaded onto the surface of PDA-ICG-PEG with high efficiency.With Mn 2+ ions intrinsically chelated, PDA-ICG-PEG/DOX(Mn) is able to offer contrast under T1-weighted magnetic resonance (MR) imaging.In a mouse tumor model, the MR imaging-guided combined chemo-& photothermal therapy achieves a remarkable synergistic therapeutic effect compared with the respective single treatment modality.This work demonstrates that PDA nanoparticles could serve as a versatile molecular loading platform for MR imaging guided combined chemo-& photothermal therapy with minimal side effects, showing great potential for cancer theranostics.

Hypoxia not only promotes tumor metastasis but also strengthens tumor resistance to therapies that demand the involvement of oxygen, such as radiation therapy and photodynamic therapy (PDT). Herein, taking advantage of the high reactivity of manganese dioxide (MnO2) nanoparticles toward endogenous hydrogen peroxide (H2O2) within the tumor microenvironment to generate O2, multifunctional chlorine e6 (Ce6) loaded MnO2 nanoparticles with surface polyethylene glycol (PEG) modification (Ce6@MnO2‐PEG) are formulated to achieve enhanced tumor‐specific PDT. In vitro studies under an oxygen‐deficient atmosphere uncover that Ce6@MnO2‐PEG nanoparticles could effectively enhance the efficacy of light‐induced PDT due to the increased intracellular O2 level benefited from the reaction between MnO2 and H2O2, the latter of which is produced by cancer cells under the hypoxic condition. Owing to the efficient tumor homing of Ce6@MnO2‐PEG nanoparticles upon intravenous injection as revealed by T1‐weighted magnetic resonance imaging, the intratumoral hypoxia is alleviated to a great extent. Thus, in vivo PDT with Ce6@MnO2‐PEG nanoparticles even at a largely reduced dose offers remarkably improved therapeutic efficacy in inhibiting tumor growth compared to free Ce6. The results highlight the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome current limitations of cancer therapies.

Nanoscale metal organic frameworks (NMOFs) have shown great potential in biomedicine owing to their structural/chemical diversities, high molecular loading capacities, and intrinsic biodegradability. Herein, we report the rational design of a NMOF composed by hafnium (Hf(4+)) and tetrakis (4-carboxyphenyl) porphyrin (TCPP). In such Hf-TCPP NMOFs, while TCPP is a photosensitizer to allow photodynamic therapy (PDT), Hf(4+) with strong X-ray attenuation ability could serve as a radio-sensitizer to enhance radiotherapy (RT). Those NMOFs with polyethylene glycol (PEG) coating show efficient tumor homing upon intravenous injection, and thus could be used for in vivo combined RT & PDT, achieving a remarkable anti-tumor effect. Importantly, Hf-TCPP NMOFs show efficient clearance from the mouse body, minimizing concerns regarding their possible long-term toxicity. Our work thus presents a new concept of developing multifunctional NMOFs as a biodegradable carrier-free system, in which both metal ions and organic ligands are fully utilized to exert their therapeutic functions.

A unique type of pH/H2 O2 dual-responsive intelligent nanoscale delivery system based on albumin-coated MnO2 is presented, which is capable of modulating the tumor microenvironment (TME) by relieving hypoxia. Additionally, TME-responsive size changes enable effective intratumor diffusion. A highly effective combined photodynamic and chemotherapy is realized with these nanoparticles in a mouse tumor model.