Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy.

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy.
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使用免疫佐剂纳米粒子的光热疗法与检查点阻断相结合,可实现有效的癌症免疫疗法

DOI:
10.1038/ncomms13193
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发表时间:
2016-10-21
影响因子:
16.6
通讯作者:
Liu, Zhuang
Liu, Zhuang
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen, Qian;Xu, Ligeng;Liang, Chao;Wang, Chao;Peng, Rui;Liu, Zhuang

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本文通过将基于辅助纳米颗粒的光热疗法与检查点阻断免疫疗法组合来开发可以消除原发性肿瘤、抑制转移和预防肿瘤复发的治疗策略。光热剂吲哚菁绿色(ICG)和Toll样受体-7激动剂咪喹莫特(R837)由聚(乳酸-共-乙醇酸)(PLGA)共包封。所形成的纯由三种临床批准的组分组成的PLGA-ICG-R837纳米颗粒可用于原发性肿瘤的近红外激光触发光热消融,产生肿瘤相关抗原,其在含有R837的纳米颗粒作为佐剂的存在下可显示疫苗样功能。与使用抗细胞毒性T淋巴细胞抗原-4(CTLA 4)的检查点阻断组合,产生的免疫应答将能够攻击小鼠中的剩余肿瘤细胞,可用于转移抑制,并且可能适用于各种类型的肿瘤模型。此外,这种策略提供了强的免疫记忆效应,其可以提供针对在消除其初始肿瘤后的肿瘤再攻击的保护。
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.
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发表时间: 2013-08-01
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