Guangdong Key Laboratory of Nanomedicine, CAS Key Lab for Health Informatics, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations , Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences , Shenzhen 518055 , P. R. China.
University of Chinese Academy of Sciences , Beijing 100049 , P. R. China.
ACS Nano. 2018 Aug 28;12(8):8633-8645. doi: 10.1021/acsnano.8b04371. Epub 2018 Jul 19.
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 tumors 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.
一种理想的癌症治疗策略，不仅需要拥有强大的能力来消融原发性肿瘤，还需要具备预防远处转移和复发的能力。在本研究中，通过分子间二硫键将人血清白蛋白与血红蛋白杂交，开发了一种新型的复合蛋白氧纳米载体，用于包载氯乙啶（C@HPOC），以实现自供氧光动力治疗（PDT）。C@HPOC 实现了光敏剂和氧气的肿瘤靶向共递药，显著缓解了肿瘤缺氧。C@HPOC 有利于更有效的 PDT，并增强了肿瘤内 CD8 T 细胞的浸润。此外，C@HPOC 增强的 PDT 通过释放危险相关分子模式来激活树突状细胞、T 淋巴细胞和自然杀伤细胞，诱导免疫原性细胞死亡。值得注意的是，C@HPOC 介导的免疫原性 PDT 通过引发全身性抗肿瘤免疫，能够破坏原发性肿瘤，并有效地抑制转移性三阴性乳腺癌模型中的远处肿瘤和肺转移。本研究为转移性癌症的治疗提供了一种增强免疫的 PDT 范例。
