A Self-Delivery Chimeric Peptide for Photodynamic Therapy Amplified Immunotherapy
A Self-Delivery Chimeric Peptide for Photodynamic Therapy Amplified Immunotherapy
复制标题
用于光动力疗法放大免疫疗法的自传递嵌合肽
DOI：
10.1002/mabi.201800410
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发表时间：
2019-04-01
影响因子：
4.6
通讯作者：
Li, Shi-Ying
中科院分区：
文献类型：
--
作者：
Cheng, Hong;Fan, Gui-Ling;Li, Shi-Ying
本文设计了一种自递式嵌合肽PpIX-PEG（8）-KVPRNQDWL，用于光动力疗法（PDT）增强免疫治疗恶性黑色素瘤。自组装成纳米粒（PPMA）后，该自释药系统具有载药率高、分散性好、稳定性好以及产生活性氧的能力。细胞摄取后，光照射下产生的ROS可诱导肿瘤细胞凋亡和/或坏死，从而刺激抗肿瘤免疫反应。另一方面，黑色素瘤特异性抗原（KVPRNQDWL）肽也可以激活特异性细胞毒性T细胞用于抗肿瘤免疫。与单独的免疫疗法相比，组合的光动力免疫疗法表现出对黑色素瘤生长的显著增强的抑制。体内外研究均证实，PPMA的PDT具有抗肿瘤免疫应答的积极作用。这种自我递送系统展示了这种PDT扩增免疫治疗策略用于晚期或转移性肿瘤治疗的巨大潜力。
In this paper, a self-delivery chimeric peptide PpIX-PEG(8)-KVPRNQDWL is designed for photodynamic therapy (PDT) amplified immunotherapy against malignant melanoma. After self-assembly into nanoparticles (designated as PPMA), this self-delivery system shows high drug loading rate, good dispersion, and stability as well as an excellent capability in producing reactive oxygen species (ROS). After cellular uptake, the ROS generated under light irradiation could induce the apoptosis and/or necrosis of tumor cells, which would subsequently stimulate the anti-tumor immune response. On the other hand, the melanoma specific antigen (KVPRNQDWL) peptide could also activate the specific cytotoxic T cells for anti-tumor immunity. Compared to immunotherapy alone, the combined photodynamic immunotherapy exhibits significantly enhanced inhibition of melanoma growth. Both in vitro and in vivo investigations confirm that PDT of PPMA has a positive effect on anti-tumor immune response. This self-delivery system demonstrates a great potential of this PDT amplified immunotherapy strategy for advanced or metastatic tumor treatment.