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多功能药物递送纳米系统释放 TLR-7 免疫刺激剂和 OKT3 诱导有效的癌症免疫治疗。

A multi-functional drug delivery nanosystem release of TLR-7 immunostimulant and OKT3 induced efficient cancer immunotherapy.

机构信息

College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.

College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.

出版信息

Photodiagnosis Photodyn Ther. 2023 Dec;44:103834. doi: 10.1016/j.pdpdt.2023.103834. Epub 2023 Oct 4.

Abstract

Immunotherapy has some shortcomings such as off-target toxicity, treatment time and poor immunogenicity, which limit its therapeutic effect. Nanomaterials are particularly attractive in immunotherapy due to their drug delivery capabilities. Nano drug delivery system loaded with Toll-like receptor (TLR) agonist imiquimod (IMQ) and CD3 immune antibody OKT3 is constructed by using polydopamine (PDA) and CaCO. While PDA-IMQ@CaCO-OKT3 (PICO NPs) drug delivery system has the advantages of high biocompatibility, low toxicity, degradability. Antitumor studies in vitro and in vivo have shown that the system can effectively inhibit the proliferation of mouse breast cancer cells and the activity of Regulatory T Cells (Tregs), activate immunogenic cell death (ICD), and enhance the activity of antigen-presenting cells (APCs). Effectively eliminate tumor immunosuppression and fully activate immune function.

摘要

免疫疗法存在一些缺点,如脱靶毒性、治疗时间长和免疫原性差,这限制了其治疗效果。由于具有药物传递能力,纳米材料在免疫疗法中特别有吸引力。通过使用聚多巴胺(PDA)和 CaCO 构建了负载 Toll 样受体(TLR)激动剂咪喹莫特(IMQ)和 CD3 免疫抗体 OKT3 的纳米药物递送系统。虽然 PDA-IMQ@CaCO-OKT3(PICO NPs)药物递送系统具有高生物相容性、低毒性、可降解性的优点。体外和体内抗肿瘤研究表明,该系统能有效抑制小鼠乳腺癌细胞的增殖和调节性 T 细胞(Tregs)的活性,激活免疫原性细胞死亡(ICD),增强抗原呈递细胞(APCs)的活性。有效消除肿瘤免疫抑制,充分激活免疫功能。

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