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靶向近红外光响应治疗性免疫纳米医学联合 TLR7 激动剂和免疫检查点阻断用于有效的癌症光热免疫治疗。

Targeted NIR-responsive theranostic immuno-nanomedicine combined TLR7 agonist with immune checkpoint blockade for effective cancer photothermal immunotherapy.

机构信息

Bio-Nano Therapeutics Research Laboratory, Cancer Research Program (CPR), Department of Zoology, School of Life Science, Bharathiar University, Coimbatore, 641 046, India.

出版信息

J Mater Chem B. 2022 Aug 24;10(33):6392-6403. doi: 10.1039/d2tb01195f.

DOI:10.1039/d2tb01195f
PMID:35971846
Abstract

Nanomedicine with immunotherapy offers opportunities to target cancer in an effective manner; however, it remains challenging. We herein report a photothermal material loaded with immune-adjuvant combined immune checkpoint blockade for efficient cancer immunotherapy to target estrogen receptor-positive (ER) breast cancer (BC). Endoxifen (END) expressly targets ER breast cancer cells. As a proof of concept of a targeting ER agent, END/NIR-responsive polyaniline (PANi)/a toll-like-receptor-7 agonist imiqumoid (R837) activating immune response co-encapsulated nanoparticles were formed as END-PANi-PVP@R837 NPs and found to be very appropriate as an NIR-responsive photothermal platform for versatile immunogenic cell death (ICD) in combination with an immune checkpoint PD-L1 blockade for development as an immunotherapy strategy. In this study, we concentrate on the therapeutic tactic of combining anti-PD-L1 with NPs, not only ablating cancer cells upon NIR irradiation but also providing strong anti-cancer immunity to destroy tumor progression after treatment. In both and experiments it was demonstrated that NPs could efficiently activate PTT to induce an immune response and immune resistance based on the PD-L1 checkpoint to ablate the tumor and inhibit tumor recurrence. We confirm the potency of the NPs, which exhibit high photothermal conversion efficacy and stability. The results demonstrate that the NP combination suppresses tumor cell growth at the tumor margin beyond effective PTT and immunotherapy.

摘要

纳米医学与免疫疗法相结合为有效地靶向癌症提供了机会;然而,这仍然具有挑战性。我们在此报告了一种负载免疫佐剂的光热材料与免疫检查点阻断联合用于有效的癌症免疫治疗,以靶向雌激素受体阳性(ER)乳腺癌(BC)。Endoxifen(END)专门针对 ER 乳腺癌细胞。作为靶向 ER 药物的概念验证,END/NIR 响应的聚苯胺(PANi)/ toll 样受体-7 激动剂咪喹莫特(R837)激活免疫反应共包封纳米颗粒被形成 END-PANi-PVP@R837 NPs,并且发现非常适合作为一种 NIR 响应光热平台,用于与免疫检查点 PD-L1 阻断联合进行多功能免疫原性细胞死亡(ICD),以开发作为免疫治疗策略。在这项研究中,我们专注于联合抗 PD-L1 与 NPs 的治疗策略,不仅在 NIR 照射下消融癌细胞,而且在治疗后提供强大的抗癌免疫来破坏肿瘤进展。在 和 实验中,证明 NPs 可以有效地激活 PTT 以诱导免疫反应和基于 PD-L1 检查点的免疫抵抗,从而消融肿瘤并抑制肿瘤复发。我们证实了 NPs 的效力,其表现出高的光热转换效率和稳定性。结果表明,NP 联合治疗在有效的 PTT 和免疫治疗之外抑制肿瘤边缘的肿瘤细胞生长。

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