School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
CAS Key Laboratory of Biomedical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science (CAS), Suzhou, 215163, China.
J Nanobiotechnology. 2022 Apr 7;20(1):181. doi: 10.1186/s12951-022-01388-8.
Cancer immunotherapy is limited by the immune escape of tumor cells and adverse effects. Photo-immunotherapy, the combination of immunotherapy and phototherapy (such as photodynamic therapy (PDT) and photothermal therapy (PTT)), can improve the effectiveness of immunotherapy in cancer treatment. Here, we first explored mesoporous hexagonal core-shell zinc porphyrin-silica nanoparticles (MPSNs), which are composed of a zinc porphyrin core and a mesoporous silica shell, and exhibit high laser-triggered photodynamic and photothermal activity, as well as outstanding drug loading capacity. In other words, MPSNs can be used not only as excellent photosensitizers for photo-immunotherapy, but also as an ideal drug carrier to achieve more efficient synergy. After loading with R837 (imiquimod, a toll-like receptor-7 agonist), MPSNs@R837 will elicit high-efficiency immunogenic cell death via PDT and PTT, and promote dendritic cell maturation after the PH-responsive release of R837, thereby, inducing tumor-specific immune responses. When combined with a programmed death ligand-1 checkpoint blockade, the photo-immunotherapy system markedly restrains primary tumors and metastatic tumors with negligible systemic toxicity. Therefore, the therapeutic strategy of integrating PTT, PDT and checkpoint blockade, shows great potential for suppressing cancer metastasis.
癌症免疫疗法受到肿瘤细胞免疫逃逸和不良反应的限制。光免疫疗法将免疫疗法与光疗(如光动力疗法(PDT)和光热疗法(PTT))相结合,可以提高癌症治疗中免疫疗法的效果。在这里,我们首次探索了介孔六方核壳锌卟啉-二氧化硅纳米粒子(MPSNs),它由锌卟啉核和介孔二氧化硅壳组成,具有高激光触发的光动力和光热活性,以及出色的载药能力。换句话说,MPSNs 不仅可以用作光免疫疗法的优秀光敏剂,还可以用作理想的药物载体,以实现更高效的协同作用。负载 R837(咪喹莫特,一种 Toll 样受体-7 激动剂)后,MPSNs@R837 通过 PDT 和 PTT 引发高效的免疫原性细胞死亡,并在 R837 的 PH 响应释放后促进树突状细胞成熟,从而诱导肿瘤特异性免疫反应。与程序性死亡配体-1 检查点阻断联合使用时,光免疫治疗系统可显著抑制原发性肿瘤和转移性肿瘤,而几乎没有全身毒性。因此,整合 PTT、PDT 和检查点阻断的治疗策略在抑制癌症转移方面显示出巨大的潜力。