摘要：photodynamic therapy(PDT)has significant advantages in treating primary ***,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer ***,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA *** nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic *** therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-***,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic *** vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and ***,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

摘要：Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D *** findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.

摘要：Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.

摘要：photodynamic therapy(PDT)as a non-invasive anticancer modality has received increasing attention due to its advantages of noninvasiveness,high temporospatial selectivity,simple and controllable operation,*** mainly relies on the generation of toxic reactive oxygen species(ROS)by photosensitizers(PSs)under the light irradiation to cause cancer cell apoptosis and ***,solid tumors usually exhibit an inherent hypoxic microenvironment,which greatly limits the PDT efficacy of these high oxygen-dependent conventional type II ***,it is of great importance to design and develop efficient type I PSs that are less oxygen-dependent for the treatment of hypoxic ***,a new strategy for the preparation of efficient type I PSs by introducing the photoinduced electron transfer(PET)mechanism is ***-NO_(2) is obtained by introducing 4-nitrobenzyl to(Z)-2-(5-(4-(diethylamino)-2-hydroxybenzylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile(DR-OH)with aggregation-induced emission(AIE)*** AIE feature ensures their high ROS generation efficiency in aggregate,and the PET process leads to fluorescence quenching of DR-NO_(2) to promote triplet state formation,which also promotes intramolecular charge separation and electron transfer that is conducive for type I ROS particularly superoxide radicals *** addition,DR-NO_(2) nanoparticles are prepared by nanoprecipitation to possess nanoscaled sizes,high cancer cell uptake,and excellent type I ROS generation ability,which results in an excellent performance in PDT ablation of MCF-7 cancer *** PET strategy for the development of type I PSs possesses great potential for PDT applications against hypoxic tumors.

摘要：Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic ***,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer ***,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide *** this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce *** glucose depletion induced"starvation"in cancer cells and caused cell ***,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 *** toxic hydroxyl radicals produced by photolysis further induced cancer cell *** in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single *** study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.

摘要：The acidic tumor microenvironment is triggered by glycolysis in hypoxic condition, which can motivate the pHresponsive system to build certain triggers for efficiently tumor-targeted phototherapy. Additionally, the metalated porphyrin structures are widely studied in biomedical applications due to the favorable properties of high singlet oxygen quantum yield as well as strong fluorescence imaging ability. Herein, a pH-responsive zinc(II) metalated porphyrin(P-4) was designed and synthesized for amplifying cancer photodynamic/photothermal therapy with excellent fluorescence quantum yield(67.4%), superb singlet oxygen quantum yield(84.3%) and desired photothermal conversion efficiency(30.0%). In vitro, the self-assembled P-4 nanoparticles can specifically target to lysosome subcellular site and realize protonated process of dibutaneaminophenyl(DBAP) groups with high photo toxicity. Under single 660 nm laser illumination, the tumor can be ablated completely with no side effects in vivo. This work demonstrates that the p H-responsive P-4 nanoparticles provide a new avenue for highly efficient cancer combination therapy.

摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (ICD). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking CD39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of ICD with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：For most organisms,molecular oxygen is indispensable for normal physiological metabolism;in humans,prolonged hypoxia in tissues can induce many diseases,exemplified by cardiovascular disease,chronic wounds,and tissue ***,the oxygen in our environment is vital for *** a main source of oxygen in the natural world that transforms light energy into chemical energy and oxygen,photosynthesis has been widely studied in scientific research and used in production of food,fuel,and *** recent years,photosynthesis has become more closely involved in biomedicine and has been widely used in photodynamic therapy,tissue regeneration,transplantation,and in treatment of specific *** review summarizes innovative applications of photosynthesis in biomedical research and highlights the theory and implications of clinical treatment for specific diseases.

摘要：The effect of tumor-targeted photodynamic therapy（PDT） was improved by designing nanotheranostics to promote oxygenation in a tumor microenvironment（TME）wherein hypoxia, acidosis, and the elevated levels of H2O2 are three main characteristics. In this study, a carbon dot（CD）PDT agent recently developed by our group was firstly applied as reducing agent to react with potassium permanganate for fabricating CDs/manganese dioxide（CDs/MnO2） composites,which were in turn modified with polyethylene glycol（PEG） to form water-soluble CDs/MnO2-PEG nanohybrids. In a normal physiological environment, the as-prepared nanohybrids exhibited quenched fluorescence, weak singlet oxygen generation, and low magnetic resonance imaging（MRI） ***, given the high sensitivity of MnO2 to the TME, the CDs/MnO2-PEG nanohybrids changed from an ＂off＂ to an＂on＂ state with synchronously enhanced fluorescence, singlet oxygen generation, and MRI signal in the TME. In vitro and in vivo analyses have revealed that CDs/MnO2-PEG nanohybrids could be applied as TME-driven, turn-on nanotheranostics for the MR/fluorescence bimodal imaging-guided PDT of ***, complete clearance of CDs/MnO2-PEG nanohybrids from the body of mice was observed, indicating their low long-term toxicity and good biocompatibility. This work offers a new nanotheranostic candidate for modulating the unfavorable TME, particularly for the targeted PDT of cancer through precise positioning and oxygen generation.