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Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3471-3488页

作者： Fan Tong Haili Hu Yanyan Xu Yang Zhou Rou Xie Ting Lei Yufan Du Wenqin Yang Siqin He Yuan Huang Tao Gong Huile Gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China

As known,the benefits of photothermal therapy(PTT)are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins(HSPs).Then HSPs further trigger the formation of stress granules(SGs)that regulate protein expression and cell viability under various stress *** of SG formation can sensitize tumor cells to ***,we developed PEGylated pH(low)insertion peptide(PEG-pHLIP)-modified hollow copper sulfide nanoparticles(HCuS NPs)encapsulating the SG inhibitor ISRIB,with the phase-change material lauric acid(LA)as a gatekeeper,to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system(IL@H-PP).The nano medicine could specifically target slightly acidic tumor *** irradiation,IL@H-PP realized PTT,and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT,thereby increasing the antitumor effect and inducing potent immunogenic cell death(ICD).Moreover,IL@H-PP could promote the production of reactive oxygen species(ROS)by tumor-associated macrophages(TAMs),repolarizing them towards the M1 phenotype and remodeling the immunosuppressive *** vitro/vivo results revealed the potential of PTT combined with SG inhibitors,which provides a new paradigm for antitumor and antimetastases.

关键词： Hollow coppersulfide nanoparticles Sensitized PTT SG inhibition TAMs repolarization pH-driven targeting photothermal responsiveness Immunotherapy Anti-metastases

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Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy,vascularization and anti-inflammation for diabetic infected wound healing

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Bioactive Materials 2023年第8期26卷 306-320页

作者： Shuangli Zhu Bangjiao Zhao Maocai Li Hao Wang Jiayi Zhu Qingtao Li Huichang Gao Qi Feng Xiaodong Cao School of Materials Science and Engineering South China University of TechnologyGuangzhou510641PR China National Engineering Research Centre for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006PR China School of Medicine South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou510006PR China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou510006PR China Zhongshan Institute of Modern Industrial Technology of SCUT ZhongshanGuangdong528437PR China

Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic *** present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic ***,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of *** this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging *** slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel *** had a pH and glucose responsive release behavior to treat different wound microenvironment ***,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long ***@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB *** experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and ***,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

关键词： Diabetic ulcer Hydrogel dressing Cu-loaded polydopamine nanoparticles Metformin photothermal responsiveness Angiogenesis and anti-inflammation

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