State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830054, China; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
Biomaterials. 2019 Jun;206:170-182. doi: 10.1016/j.biomaterials.2019.03.027. Epub 2019 Mar 22.
Photodynamic therapy (PDT) has attracted growing attention in the field of cancer therapy due to its non-invasive intervention and initiation of antitumor immune responses by use of non-toxic photosensitizers (PS) and topical light irradiation. However, inherent hypoxia and immunosuppression mediated by checkpoints in tumors severally impair the efficacy of PDT and PDT-induced immunity. Herein, a multi-functional nanoplatform is rationally constructed by fluorinated polymer nanoparticle saturated with oxygen in advance, which simultaneously encapsulated PS (Ce6) and an indoleamine 2,3-dioxygenase (IDO) inhibitor (NLG919). In particular, the tumor hypoxic microenvironment is obviously relieved and much more reactive oxygen species (ROS) is generated by fluorinated nanoparticle compared with alkylated polymer nanoparticle as a control in vitro and in vivo, this is mainly because the fluorinated polymers are endowed with high oxygen carrying capacity which also contributed to the relief of hypoxia. Meanwhile, compared to PDT alone, the co-encapsulation of IDO inhibitor and PS can further greatly enhance efficacy for inhibiting the growth of primary and abscopal tumors via enhanced T cell infiltration. This study can provide a convenient and practical strategy for enhancing the therapeutic effect of PDT and relieving immune suppression, in turn affording clinical benefits for cancer treatment.
光动力疗法（PDT）因其使用无毒的光敏剂（PS）和局部光照射进行非侵入性干预和引发抗肿瘤免疫反应而在癌症治疗领域受到越来越多的关注。然而，肿瘤中由检查点介导的固有缺氧和免疫抑制分别严重损害了 PDT 的疗效和 PDT 诱导的免疫。在此，通过预先用氟聚合物纳米粒子饱和氧气来合理构建多功能纳米平台，该纳米平台同时包封了 PS（Ce6）和吲哚胺 2,3-双加氧酶（IDO）抑制剂（NLG919）。特别是与作为对照的烷基化聚合物纳米粒子相比，氟化物纳米粒子在体外和体内明显缓解了肿瘤缺氧微环境，并产生了更多的活性氧（ROS），这主要是因为氟聚合物具有高携氧能力，这也有助于缓解缺氧。同时，与单独的 PDT 相比，IDO 抑制剂和 PS 的共包封可以通过增强 T 细胞浸润，进一步大大增强抑制原发性和远隔肿瘤生长的疗效。本研究为增强 PDT 的治疗效果和缓解免疫抑制提供了一种方便实用的策略，进而为癌症治疗带来临床获益。
