光动力疗法
光敏剂
化学
癌症研究
免疫原性细胞死亡
肿瘤缺氧
肿瘤微环境
活性氧
免疫系统
程序性细胞死亡
免疫学
生物化学
医学
细胞凋亡
放射治疗
内科学
有机化学
肿瘤细胞
作者
Bingchen Zhang,Gang Li,Jizong Mao,Weisheng Mo,Zibo Li,Shengtao Wang,Yan Tang,Chunhui Cui,Yifen Wu,Zhiqiang Yu
标识
DOI:10.1016/j.cclet.2023.108518
摘要
Photodynamic therapy (PDT) has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death (ICD) effects. However, the strategy is limited in the innate hypoxic tumor microenvironment. There are two key elements for the realization of enhanced PDT: specific cellular uptake and release of the photosensitizer in the tumor, and a sufficient amount of oxygen to ensure photodynamic efficiency. Herein, self-oxygenated biomimetic nanoparticles (CS@M NPs) co-assembled by photosensitizer prodrug (Ce6-S-S-LA) and squalene (SQ) were engineered. In the treatment of triple negative breast cancer (TNBC), the oxygen carried by SQ can be converted to reactive oxygen species (ROS). Meanwhile, glutathione (GSH) consumption during transformation from Ce6-S-S-LA to chlorin e6 (Ce6) avoided the depletion of ROS. The co-assembled (CS NPs) were encapsulated by homologous tumor cell membrane to improve the tumor targeting. The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin (CRT) and high mobility group protein B1 (HMGB1), and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha (HIF-1α)-CD39-CD73-adenosine a2a receptor (A2AR) pathway, which not only promoted the maturation of dendritic cells (DC) and the presentation of tumor specific antigens, but also induced effective immune infiltration of tumors. Overall, the integrated nanoplatform implements the concept of multiple advantages of tumor targeting, reactive drug release, and synergistic photodynamic therapy-immunotherapy, which can achieve nearly 90% tumor suppression rate in orthotopic TNBC models.
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