Ex vivo generation of functional immune cells by mitochondria-targeted photosensitization of cancer cells.
Ex vivo generation of functional immune cells by mitochondria-targeted photosensitization of cancer cells.
复制标题
通过癌细胞的线粒体靶向光敏作用离体产生功能性免疫细胞。
DOI：
10.1007/978-1-4939-2288-8_9
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Dhar,Shanta
中科院分区：
文献类型：
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作者：
Marrache,Sean;Tundup,Smanla;Harn,DonaldA;Dhar,Shanta
刺激免疫系统进行有效的癌症免疫治疗是一种潜在的革命性的根除癌症的方法。用光敏剂（ps）刺激肿瘤不仅能杀死癌细胞，还有助于增强免疫系统。我们最近报道了肿瘤相关抗原（TAAs）的产生，通过线粒体作用的PS锌酞菁（ZnPc）传递到MCF-7乳腺癌细胞，随后激光照射可导致小鼠骨髓源性树突状细胞（bmdc）的体外刺激。从乳腺癌细胞中产生的抗原也被发现引起显著的DC成熟，激活的DC能够刺激T细胞成为细胞毒性CD8+T细胞。在该方案中，我们描述了设计线粒体靶向可生物降解纳米颗粒（NP）配方的方法，将ZnPc递送到MCF-7细胞的线粒体的T-ZnPc-NPs，随后使用长波激光照射产生TAAs的光动力治疗（PDT）， TAAs刺激DC分泌干扰素γ (IFN-γ)，以及成熟DC驱动t细胞活化的方法。
Stimulating the immune system for potent immune therapy against cancer is potentially a revolutionary method to eradicate cancer. Tumors stimulated with photosensitizers (PSs) not only kill cancer cells but also help to boost the immune system. We recently reported that tumor-associated antigens (TAAs) generated by delivery of a mitochondria-acting PS zinc phthalocyanine (ZnPc) to MCF-7 breast cancer cells followed by laser irradiation can lead to ex vivo stimulation of mouse bone marrow-derived dendritic cells (BMDCs). The antigens generated from the breast cancer cells were also found to cause significant DC maturation and the activated DCs were able to stimulate T cells to cytotoxic CD8+T cells. In this protocol, we describe methods to engineer a mitochondria-targeted biodegradable nanoparticle (NP) formulation, T-ZnPc-NPs for delivery of ZnPc to the mitochondria of MCF-7 cells, subsequent photodynamic therapy (PDT) using a long wavelength laser irradiation to produce TAAs, DC stimulation by the TAAs to secrete interferon-gamma (IFN-γ), and matured DC-driven T-cell activation.