Bioinspired Hybrid Protein Oxygen Nanocarrier Amplified Photodynamic Therapy for Eliciting Anti-tumor Immunity and Abscopal Effect
Bioinspired Hybrid Protein Oxygen Nanocarrier Amplified Photodynamic Therapy for Eliciting Anti-tumor Immunity and Abscopal Effect
复制标题
仿生混合蛋白氧纳米载体放大光动力疗法引发抗肿瘤免疫和远隔效应
DOI：
10.1021/acsnano.8b04371
复制
发表时间：
2018-08-01
期刊：
影响因子：
17.1
通讯作者：
Cai, Lintao
中科院分区：
文献类型：
--
作者：
Chen, Zhikuan;Liu, Lanlan;Cai, Lintao
一个理想的肿瘤治疗策略应该具有强大的能力，不仅能消融原发肿瘤，还能防止远处转移和复发。本研究通过分子间二硫键将人血清白蛋白与血红蛋白进行分子间二硫键杂化，制备了一种包覆氯e6的杂化蛋白氧纳米载体(C@HPOC)，用于氧气自给式光动力疗法(PDT)。C@HPOC实现了光敏剂和氧气的肿瘤靶向共传递，显著缓解了肿瘤缺氧。C@HPOC有利于提高PDT的效率，增强CD8(+)T细胞在肿瘤中的浸润。此外，氧增强的C@HPOC的PDT诱导免疫原性细胞死亡，释放危险相关的分子模式，激活体内的树突状细胞、T淋巴细胞和自然杀伤细胞。值得注意的是，C@HPOC介导的免疫原性PDT可以通过激发全身抗肿瘤免疫，在转移性三阴性乳腺癌模型中摧毁原发肿瘤，并有效地抑制远处转移和肺转移。本研究为转移性肿瘤的氧增强型免疫原性光动力疗法提供了一个范例。
An ideal cancer therapeutic strategy is expected to possess potent ability to not only ablate primary tumors but also prevent distance metastasis and relapse. In this study, human serum albumin was hybridized with hemoglobin by intermolecular disulfide bonds to develop a hybrid protein oxygen nanocarrier with chlorine e6 encapsulated (C@HPOC) for oxygen self-sufficient photodynamic therapy (PDT). C@HPOC realized the tumor-targeted co-delivery of photosensitizer and oxygen, which remarkably relieved tumor hypoxia. C@HPOC was favorable for more efficient PDT and enhanced infiltration of CD8(+) T cells in tumors. Moreover, oxygen-boosted PDT of C@HPOC induced immunogenic cell death, with the release of danger-associated molecular patterns to activate dendritic cells, T lymphocytes, and natural killer cells in vivo. Notably, C@HPOC-mediated immunogenic PDT could destroy primary tumors and effectively suppress distant and lung metastasis in a metastatic triple-negative breast cancer model by evoking systemic anti-tumor immunity. This study provides a paradigm of oxygen augmented immunogenic PDT for metastatic cancer treatment.