Wang Zhichao, Tang Yuqi, Li Quan
Institute of Advanced Materials and School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
Materials Science Graduate Program, Kent State University, Kent, OH, 44242, USA.
Light Sci Appl. 2025 Jan 2;14(1):16. doi: 10.1038/s41377-024-01673-1.
The microenvironment of immunosuppression and low immunogenicity of tumor cells has led to unsatisfactory therapeutic effects of the currently developed nanoplatforms. Immunogenic cell death, such as pyroptosis and ferroptosis, can efficiently boost antitumor immunity. However, the exploration of nanoplatform for dual function inducers and combined immune activators that simultaneously trigger pyroptosis and ferroptosis remains limited. Herein, a multifunctional pH-responsive theranostic nanoplatform (M@P) is designed and constructed by self-assembly of aggregation-induced emission photosensitizer MTCN-3 and immunoadjuvant Poly(I: C), which are further encapsulated in amphiphilic polymers. This nanoplatform is found to have the characteristics of cancer cell targeting, pH response, near-infrared fluorescence imaging, and lysosome targeting. Therefore, after targeting lysosomes, M@P can cause lysosome dysfunction through the generation of reactive oxygen species and heat under light irradiation, triggering pyroptosis and ferroptosis of tumor cells, achieving immunogenic cell death, and further enhancing immunotherapy through the combined effect with the immunoadjuvant Poly(I: C). The anti-tumor immunotherapy effect of M@P has been further demonstrated in in vivo antitumor experiment of 4T1 tumor-bearing mouse model with poor immunogenicity. This research would provide an impetus as well as a novel strategy for dual function inducers and combined immune activators enhanced photoimmunotherapy.
肿瘤细胞的免疫抑制和低免疫原性微环境导致目前开发的纳米平台治疗效果不尽人意。免疫原性细胞死亡,如焦亡和铁死亡,可有效增强抗肿瘤免疫力。然而,同时触发焦亡和铁死亡的双功能诱导剂和联合免疫激活剂的纳米平台探索仍然有限。在此,通过聚集诱导发光光敏剂MTCN-3和免疫佐剂聚肌胞苷酸(Poly(I:C))的自组装设计并构建了一种多功能pH响应型诊疗纳米平台(M@P),它们进一步被封装在两亲性聚合物中。发现该纳米平台具有癌细胞靶向、pH响应、近红外荧光成像和溶酶体靶向的特性。因此,靶向溶酶体后,M@P可通过光照下产生活性氧和热量导致溶酶体功能障碍,触发肿瘤细胞的焦亡和铁死亡,实现免疫原性细胞死亡,并通过与免疫佐剂聚肌胞苷酸(Poly(I:C))的联合作用进一步增强免疫治疗。M@P的抗肿瘤免疫治疗效果在免疫原性较差的4T1荷瘤小鼠模型的体内抗肿瘤实验中得到了进一步验证。该研究将为双功能诱导剂和联合免疫激活剂增强光免疫治疗提供动力和新策略。