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可注射温敏水凝胶增强乳腺肿瘤的光热消融和系统免疫治疗。

Injectable thermosensitive hydrogel to enhance the photothermal ablation and systemic immunotherapy of breast tumors.

机构信息

School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, P.R. China.

出版信息

Biomater Sci. 2022 Oct 11;10(20):6003-6012. doi: 10.1039/d2bm01037b.

Abstract

As the high-frequency tumor in women around the world, breast cancer has high mortality due to metastasis tumors making it difficult to cure. Herein, we report a near-infrared (NIR) activated bio-multifunctional thermosensitive hydrogel (denoted as AMDR) with powerful cell killing and immunogenicity amplifying ability. Based on the molecular engineering strategy, a photothermal agent (M-4) with 52.4% conversion efficiency was synthesized. Accordingly, the designed injectable thermosensitive hydrogel AMDR is simply fabricated by the employment of the M-4 photothermal agent, doxorubicin hydrochloride (DOX) as the antitumor drug, and imiquimod (R837) as the immunologic adjuvant by self-assembly. Under NIR irradiation, the AMDR hydrogel can generate local mild heat to release DOX for synergistic killing of tumor cells with little damage to normal cells. The immunogenic cell death induced by potent killing combined with heat-released R837 can trigger robust immune response to inhibit and kill metastasis tumors. The developed AMDR hydrogel is successfully applied in the treatment of primary tumors and inhibition of distal tumors of tumor-bearing mice. The study provides a novel strategy and platform for complete treatment of breast cancer and also offers ideas for designing high-efficiency photothermal agents.

摘要

作为全球女性高发的高频肿瘤,乳腺癌由于转移肿瘤导致死亡率高,难以治愈。在此,我们报告了一种近红外(NIR)激活的生物多功能热敏水凝胶(表示为 AMDR),具有强大的细胞杀伤和免疫原性放大能力。基于分子工程策略,合成了一种光热剂(M-4),其转化率为 52.4%。相应地,通过使用 M-4 光热剂、盐酸多柔比星(DOX)作为抗肿瘤药物和咪喹莫特(R837)作为免疫佐剂自组装,简单制备了设计的可注射热敏水凝胶 AMDR。在近红外照射下,AMDR 水凝胶可以产生局部温和的热量,以释放 DOX,从而协同杀伤肿瘤细胞,而对正常细胞的损伤很小。强大的杀伤作用和热释放的 R837 诱导的免疫原性细胞死亡可引发强烈的免疫反应,从而抑制和杀死转移肿瘤。所开发的 AMDR 水凝胶成功地应用于荷瘤小鼠的原发性肿瘤治疗和远端肿瘤抑制。该研究为乳腺癌的完全治疗提供了一种新的策略和平台,并为设计高效光热剂提供了思路。

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