Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Nat Commun. 2016 Oct 21;7:13193. doi: 10.1038/ncomms13193.
A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.
本文提出了一种治疗策略,即结合辅助性基于纳米粒子的光热疗法和检查点阻断免疫疗法,以消除原发性肿瘤、抑制转移和预防肿瘤复发。将吲哚菁绿(ICG)作为光热试剂和咪喹莫特(R837)作为 Toll 样受体-7 激动剂共同包封于聚乳酸-羟基乙酸共聚物(PLGA)中。所形成的 PLGA-ICG-R837 纳米颗粒完全由三种临床批准的成分组成,可用于近红外激光触发的原发性肿瘤光热消融,产生肿瘤相关抗原,在含有 R837 的纳米颗粒作为佐剂的情况下,这些抗原具有疫苗样的功能。与使用抗细胞毒性 T 淋巴细胞抗原-4(CTLA4)的检查点阻断联合使用,所产生的免疫反应将能够攻击小鼠体内的剩余肿瘤细胞,从而有效抑制转移,并且可能适用于各种类型的肿瘤模型。此外,该策略提供了强大的免疫记忆效应,可在消除初始肿瘤后提供对肿瘤再挑战的保护。