工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Nanomedicine carrier-based combined antitumor strategy integrating phototherapy and immunotherapy.
Nanomedicine carrier-based combined antitumor strategy integrating phototherapy and immunotherapy.
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尽管临床前研究取得了令人瞩目的成功,但临床转化仍面临挑战,包括生产可扩展性、人类肿瘤异质性以及最佳治疗顺序。
引言:光疗(光热治疗 PTT/光动力治疗 PDT)与免疫治疗联合用于癌症具有前景,但受时空协同不足和靶向共递送效果不佳的限制。纳米药物载体可精准控制药物释放动力学并降低脱靶毒性,为克服这些障碍提供平台。本综述系统分析纳米载体介导的光疗-免疫治疗联合策略的原理、机制和近期进展,重点关注过去 3 年发表的研究,并考察纳米载体如何实现靶向共递送、刺激响应释放,以及提高光疗药物和免疫调节剂在肿瘤中的蓄积。 结果:光疗可诱导免疫原性细胞死亡(ICD),其特征包括钙网蛋白暴露、ATP 分泌和高迁移率族蛋白 1(HMGB1)释放;这些变化可启动树突状细胞并引发适应性免疫。纳米载体有助于精准协调这些信号的时空过程,并实现与免疫检查点抑制剂、原位疫苗、免疫调节剂及过继性细胞疗法(包括嵌合抗原受体 CAR-T)的共递送。临床前模型中的主要结果包括将“冷”肿瘤转变为“热”肿瘤、增强 T 细胞浸润、产生远隔效应并建立持久免疫记忆。新兴趋势包括多重响应纳米平台、仿生设计,以及克服缺氧、恢复抗肿瘤免疫的策略。 讨论:尽管临床前结果令人鼓舞,临床转化仍面临生产规模化、人类肿瘤异质性和最佳治疗顺序等挑战。未来方向包括个体化纳米平台、多模式协同,以及整合人工智能和合成生物学。总之,纳米载体介导的光疗-免疫治疗整合是一种强效且不断发展的策略,有望实现持久抗肿瘤免疫,并对实体瘤治疗产生变革性影响。
INTRODUCTION: The combination of phototherapy (PTT/PDT) and immunotherapy holds promise for cancer treatment but is hindered by poor spatiotemporal coordination and inadequate targeted co-delivery. Nanomedicine carriers offer a platform to overcome these barriers by enabling precise control over drug release kinetics and reducing off-target toxicity. Methods This review systematically analyzes the rationale, mechanisms, and recent advances in nanocarrier-mediated phototherapy-immunotherapy combination strategies, with a focus on studies published within the last three years. We examine how nanocarriers enable targeted co-delivery, stimuli-responsive release, and enhanced tumor accumulation of phototherapeutic agents and immunomodulators. RESULTS: Phototherapy induces immunogenic cell death (ICD) characterized by calreticulin exposure, ATP secretion, and high-mobility group box 1 (HMGB1) release, which primes dendritic cells and initiates adaptive immunity. Nanocarriers facilitate precise spatiotemporal orchestration of these signals and enable co-delivery with immune checkpoint inhibitors, in situ vaccines, immunomodulators, and adoptive cell therapies, including chimeric antigen receptor (CAR)-T cells. Key outcomes include conversion of "cold" to "hot" tumors, enhanced T-cell infiltration, abscopal effects, and durable immune memory in preclinical models. Emerging trends include multi-responsive nanoplatforms, biomimetic designs, and hypoxia-overcoming strategies that restore antitumor immunity. DISCUSSION: Despite compelling preclinical success, challenges remain in clinical translation, including manufacturing scalability, human tumor heterogeneity, and optimal treatment sequencing. Future directions point towards personalized nanoplatforms, multimodal synergy, and the integration of artificial intelligence and synthetic biology. In conclusion, nanocarrier-mediated phototherapy-immunotherapy integration offers a powerful and evolving approach to achieve durable antitumor immunity and holds transformative potential for solid tumor treatment.
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