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：J-aggregates of cyanine have shown great merits in tumor photothermal therapy(PTT)due to their distinct redshift absorption as well as superior photothermal conversion efficiency(PCE).However,due to the complexity of intermolecular interactions,especially the impact of steric hindrance on aggregation,exploring effective strategies to regulate the aggregation modes of organic materials remains ***,steric hindrance-regulated J-aggregation of near-infrared(NIR)cyanine was reported based on Pt-coordinated cyanine self-assembly with unexpected“butterfly effect”.Two Pt-coordinated cyanine dimers CyR-Pt(R=Me and Et)were synthesized and spontaneously self-assembled into aggregates in aqueous ***-Pt aggregates were loose and amorphous *** replacing ethyl with methyl to reduce steric hindrance,a tiny change resulted in the generation of tightly stacked cyanine J-aggregates(thickness less than 3 nm)observed in CyMe-Pt ***,this unexpected“butterfly effect”enabled CyMe-Pt J-aggregates to effectively inhibit reactive oxygen species and greatly improve its ***,CyMe-Pt J-aggregates with NIR-II absorption exhibited outstanding photothermal stability and higher PCE(η=37%)than CyEt-Pt disordered aggregates(η=20%).Evident tumor suppression performance of CyMe-Pt J-aggregates was validated under 980 nm laser irradiation,demonstrating its great potential in tumor PTT.

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：The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic *** this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region photothermal transition agents(PTAs),and carriers of photosensitizer chlorin e6(Ce6)to synthesize a composite nanosystem *** this system,Pt-Ce6 can continuously and stably decompose H2O2 into oxygen,thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy(PDT).With 650 nm illumination,the reactive oxygen species(ROS)produced by Ce6 will decrease the mitochondrial membrane potential(MMP,ΔΨm)to release cytochrome c(Cyt-c)from the mitochondria into the cytoplasm,eventually leading to mitochondrial-mediated cellular apoptosis during the PDT *** addition,Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency(52.62%)in the NIR-II *** U14 tumor-bearing mice,Pt-Ce6 completely suppressed tumor growth and recurrence under laser *** the nanocomposite shows excellent PDT/photothermal therapy(PTT)synergistic performance in vitro and in vivo.

摘要：The continuous emergence of drug-resistant bacteria has become a serious threat to human and animal *** new non-antibiotic therapeutic drugs with high efficiency and low resistance is a promising strategy for combating drug-resistant ***,a novel composite structure based on a hollow metal-organic framework(MOF)wrapped Au nanorod and loaded Pt nanoparticles(Au NR@H-ZIF-8@Pt)is designed for combating drug-resistant *** Au NR@H-ZIF-8@Pt composite structures serve a twofold purpose:(1)showing superior photothermal conversion efficiency under near-infrared light irradiation,thus achieving an antibacterial effect based on photothermal effect,and(2)exhibiting high-efficiency peroxidase-like activity,and effectively killing bacteria by reactive oxygen species(ROS)generated in *** combining photothermal and catalytic effects for in vitro antibacterial experiments,Au NR@H-ZIF-8@Pt exhibits efficient,rapid,broad-spectrum antibacterial activity(99.7%for Pseudomonas aeruginosa and 98.3%for Staphylococcus aureus).In addition,in vivo experiments further demonstrate the advantages of the material in promoting bacterial infection wound *** study not only facilitates the design of novel biological nanomaterials,but also provides new ideas for combating drug-resistant bacteria.

摘要：开发近红外二区(NIR-Ⅱ)响应的纳米制剂用于NIR-Ⅱ光声成像(PAI)引导的光热治疗(PTT)为推进深层组织光诊疗的发展提供了机遇.尽管半导体聚合物纳米颗粒(SPNs)在NIR-ⅡPAI和PTT中展现出巨大的应用潜力,但其有限的光声/光热效能使得实现高效的体内光诊疗仍然是一个巨大的挑战.本工作中,我们提出了一种基于非共价键构象锁(NCL)的分子工程策略来优化SPN的NIR-Ⅱ光声/光热性能,以实现高效的体内光诊疗.NCL的引入有助于改善半导体聚合物主链的平面性,增强其捕光能力,从而提高NIR-Ⅱ光声/光热信号的输出.优化出的SPN3毒性低、尺寸合适、光物理性能好,不仅能被4T1癌细胞有效摄取并在NIR-Ⅱ光激发下杀死细胞,而且经全身给药后可通过NIR-ⅡPAI点亮肿瘤轮廓,进一步指导NIR-ⅡPTT的进行以实现高效的肿瘤热消融.因此本文的研究提供了一种独特的分子设计策略来放大SPN的NIR-Ⅱ光声/光热信号,最终实现活体高效光诊疗.