Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
Department of Hepatobiliary and Pancreatic Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
Biomaterials. 2020 Feb;232:119699. doi: 10.1016/j.biomaterials.2019.119699. Epub 2019 Dec 19.
Here, we developed platelet membranes (PM) as nano-carriers to co-encapsulate metformin (Met) and IR780 (PM-IR780-Met NPs). The resulting nano-carrier ensured a longer circulation lifetime and facilitated the greater accumulation of IR780 and Met in tumors owing to the active adhesion between PM and tumor cells. As a photodynamic therapy (PDT) agent, IR780 could effectively kill the tumor by producing toxic reactive singlet oxygen species (ROS), while the introduction of Met inhibited mitochondrial respiration and reduced tumor oxygen consumption, thereby evoking an oxygen-boosted PDT and propelling the immunogenic cell death (ICD)-based immunogenic pathway. Meanwhile, the reversed tumor hypoxia also impeded the myeloid derived suppressor cell (MDSC)-regulated immunosuppressive pathway. Finally, tremendous T cells were recruited and activated, providing a promising platform to eliminate the primary tumors and synchronously opening a new avenue for the effective ablation of tumor metastasis.
在这里，我们开发了血小板膜（PM）作为纳米载体，共同包封二甲双胍（Met）和 IR780（PM-IR780-Met NPs）。由于 PM 与肿瘤细胞之间的主动黏附，所得纳米载体确保了更长的循环寿命，并促进了 IR780 和 Met 在肿瘤中的更大积累。作为一种光动力疗法（PDT）试剂，IR780 通过产生有毒的活性单线态氧（ROS）有效杀死肿瘤，而 Met 的引入抑制了线粒体呼吸并降低了肿瘤耗氧量，从而引发了氧气增强的 PDT，并推动了基于免疫原性细胞死亡（ICD）的免疫原性途径。同时，逆转的肿瘤缺氧也阻碍了髓源抑制细胞（MDSC）调节的免疫抑制途径。最后，大量的 T 细胞被募集和激活，为消除原发性肿瘤提供了一个有前途的平台，并为有效消融肿瘤转移开辟了新途径。
