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关键词： bacteria outer membrane   oxygen gels   tumor hypoxia   radiotherapy   systemic immune response  

摘要： Radiotherapy (RT) is considered a standard cancer treatment that directly kills tumor cells and promotes a systemic immune response. However, RT may also lead to tumor hypoxia, which further inhibits the antigen-presenting function of dendritic cells (DCs) and thereby weakens the systemic anti-tumor immune response induced by radiotherapy. In this study, the oxygen-loaded in situ gels carrying bacterial outer membrane (MOGel) were synthesized. As the gels slowly degraded, oxygen was gradually released to alleviate tumor hypoxia. The released bacterial outer membrane (OM) continuously activated DCs, enhancing their antigen-presenting capability. The results demonstrated that MOGel combined with RT induced the strongest tumor cell apoptosis in vitro and achieved a 80% tumor suppression rate in a colon cancer orthotopic model. Importantly, MOGel+RT induced an enhanced abscopal effect, and hypoxia and enhanced DCs activation contributed to the systemic immune response. Thus, OM-based oxygen gels may offer a novel strategy for enhancing the systemic immune response to RT. (sic)(sic)(sic)(sic)(RT)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) (sic)(sic)(sic)(sic)(sic)(sic)(sic). (sic)RT(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(DC) (sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)RT(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic). (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) (sic)(sic)(sic)(sic)(sic)(sic)(sic)MOGel, (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(OM). (sic)(sic)(sic)(sic)(sic) (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)OM(sic)(sic)(sic) (sic)(sic)DC(sic)(sic). (sic)(sic)(sic)(sic), MOGel(sic)(sic)RT(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic) (sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)80%(sic)(sic)(sic)(sic)(

关键词： immune-phototherapy   immunogenic cell death   PANoptosis   acceptor-donor-acceptor   near infrared  

摘要： It remains a major challenge in phototherapeutics to achieve a high quantum yield of singlet oxygen generation and efficient photothermal conversion using a single near-infrared laser for immuno-phototherapy. To bridge this gap, we utilized an acceptor-donor-acceptor (A-D-A) structured molecule, 3,9-bis(2-methylene-((3-(1,1-dicyanomethylene)-6/7-methyl)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2 ',3 '-d ']-s-indaceno[1,2-b:5,6-b ']-dithiophene (m-ITIC), and formulated it into nanoparticles (NPs) by assembling with distearoylphosphatidylethanolamine-polyethylene glycol-amino (DSPE-PEG-NH2). At 688 and 768 nm, these NPs present significant near-infrared absorption and fluorescence. They simultaneously generate heat, O-2(-), and O-1(2), with the O-1(2) generation quantum yield of 56.8% and photothermal conversion efficiency (PCE) of 27.4%, enabling them excellent near-infrared (NIR) fluorescence imaging guided synergic photodynamic therapy (PDT) and photothermal therapy (PTT) capabilities. Importantly, this nanoplatform induces PANoptosis, a coordinated cell death program integrating pyroptosis, apoptosis, and necroptosis, in tumor cells, thereby amplifying immunogenic cell death (ICD) and enhancing antitumor immune responses. The combined effects lead to robust dendritic cell activation, macrophage polarization toward the M1 phenotype, elevated CD8+ T cell infiltration, and suppression of immunosuppressive Treg cells, resulting in significant tumor growth inhibition and prevention of lung metastasis in vivo. Furthermore, the therapeutic efficacy was validated in patient-derived tumor organoids, demonstrating translational potential. This study presents a novel strategy for NIR light-guided cancer phototherapy, wherein a single laser-activated nanoplatform simultaneously mediates efficient photothermal and photodynamic effects and induces PANoptosis driven ICD for synergistic cancer immunotherapy.

关键词： 碳点   pH响应   溶酶体逃逸   阿霉素释放  

关键词： 国家自然科学基金委员会   中药抗肿瘤药理   资助项目   研究方向  

关键词： 自噬   耐药性   消化道肿瘤  

关键词： photoacoustic therapy   self-collapsing   physical ablation   chemical intervention   oxidative stress  

摘要： Circumventing the tumor's defensive antioxidant system and achieving precision cancer therapy are the major challenges in achieving high-efficacy tumor treatments. In this study, we propose a rational and effective therapeutic strategy by synergistically integrating the effects of a non-oxidative physical ablation and an oxidative chemical intervention. An acid-responsive self-collapsing nanomineral PCSB is constructed, which consists of a poly(acrylic acid) (PAA)-modified calcium sulfite (CaSO3) and a pH-responsive photoacoustic (PA) therapeutic molecule, aza-BDP. The tumor acidic microenvironment promotes the decomposition of PCSB, triggering the release of PA agents and SO2/Ca2+, thereby achieving the synergistic therapy of non-oxidative mechanical damage from PA therapeutic effect and oxidative chemical damage from SO2 gas and Ca2+ metal ion therapeutic effects. Therefore, this study presents a synergistic physical and chemical treatment strategy, which shows significant potential for reducing the resistance conferred by the antioxidant mechanisms of tumor cells and improving the precision of treatment.

关键词： DNA甲基化   肿瘤   DNA甲基转移酶   脱甲基酶   分子靶向治疗   抗肿瘤药   基因表达调控   表观遗传学