School of Pharmaceutical Science, Key Laboratory of Chemical Biology (Ministry of Education) , Shandong University , Jinan , Shandong Province 250012 , P.R. China.
Key Laboratory of Colloid and Interface Chemistry (Ministry of Education) , Shandong University , Jinan , 250100 , P.R. China.
Nano Lett. 2019 Sep 11;19(9):6647-6657. doi: 10.1021/acs.nanolett.9b02923. Epub 2019 Aug 19.
The antitumor immune response involves a cascade of three phases, namely, antigen presentation (Phase I), lymphocyte activation and proliferation/differentiation (Phase II), and tumor elimination (Phase III). Therefore, an ideal immunotherapy nanoplatform is one that can simultaneously execute these three phases. However, it is of great challenge to develop a single immunotherapy nanoplatform which can deliver individual immunoagent to their on-demand target sites for simultaneously tailoring three phases because of the different target sites restricted by three phases. Herein, for the first time we reported a three-in-one immunotherapy nanoplatform that can simultaneously execute these three phases. Chlorin e6 (Ce6)-conjugated hyaluronic acid (HC), dextro-1-methyl tryptophan (1-mt)-conjugated polylysine (PM) and anti-PD-L1 monoclonal antibodies (aPD-L1) were rationally designed as aPD-L1@HC/PM NPs via an assembling strategy. The step-by-step detachment of the antigen from near-infrared light irradiated HC component, the indoleamine-pyrrole 2,3-dioxygenase (IDO) pathway inhibitor 1-mt, and the anti-PD-L1 toward their on-demand target sites demonstrated the simultaneous tailoring of Phase I, Phase II, and Phase III, respectively, of the immunotherapy. The aPD-L1@HC/PM NPs were verified to be an excellent immunotherapy nanoplatform against tumor metastasis, relapse, and postsurgical regrowth because of the cascade-amplifying cancer-immunity cycle. The present all-immunity-phase-boosted immunotherapy strategy is of great interest for designing excellent immunotherapy treatments.
抗肿瘤免疫反应涉及三个阶段的级联反应，即抗原呈递（I 期）、淋巴细胞激活和增殖/分化（II 期）以及肿瘤消除（III 期）。因此，理想的免疫治疗纳米平台应该能够同时执行这三个阶段。然而，开发一种能够将单个免疫制剂递送到其按需靶位以同时定制三个阶段的单一免疫治疗纳米平台极具挑战性，因为这三个阶段受到不同靶位的限制。在此，我们首次报道了一种三效合一的免疫治疗纳米平台，能够同时执行这三个阶段。通过组装策略，将氯乙酮（Ce6）缀合的透明质酸（HC）、右旋-1-甲基色氨酸（1-mt）缀合的聚赖氨酸（PM）和抗 PD-L1 单克隆抗体（aPD-L1）合理设计为 aPD-L1@HC/PM NPs。近红外光照射 HC 组件、色氨酸 2,3-双加氧酶（IDO）途径抑制剂 1-mt 和抗 PD-L1 从抗原的逐步分离，分别显示了免疫治疗的 I 期、II 期和 III 期的同时定制。由于级联放大的癌症免疫周期，aPD-L1@HC/PM NPs 被证明是一种出色的抗肿瘤转移、复发和术后再生长的免疫治疗纳米平台。本研究提出的全免疫阶段增强免疫治疗策略为设计优异的免疫治疗方法提供了重要思路。
