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砷配合物修饰的膜伪装仿生纳米平台用于协同增强肝癌治疗

Membrane-camouflaged biomimetic nanoplatform with arsenic complex for synergistic reinforcement of liver cancer therapy.

机构信息

Shenyang Pharmaceutical University, Shenyang, 110016, China.

Liaoning University, Shenyang, 110036, China.

出版信息

Nanomedicine (Lond). 2024;19(26):2187-2210. doi: 10.1080/17435889.2024.2393076. Epub 2024 Sep 4.

Abstract

Arsenic has excellent anti-advanced liver cancer effects through a variety of pathways, but its severe systemic toxicity forces the need for a safe and effective delivery strategy. Based on the chelating metal ion properties of polydopamine (PDA), arsenic was immobilized on an organic carrier, and a M1-like macrophage cell membrane (MM)-camouflaged manganese-arsenic complex mesoporous polydopamine (MnAsOx@MP@M) nanoplatform was successfully constructed. MnAsOx@MP@M was evaluated at the cellular level for tumor inhibition and tumor localization, and for its anti-liver cancer effect in a Hepa1-6 tumor-bearing mouse model. The nanoplatform targeted the tumor site through the natural homing property of MM, completely degraded and released drugs to kill tumor cells in an acidic environment, while playing an immunomodulatory role in promoting tumor-associated macrophages (TAMs) repolarization. MnAsOx@MP@M has synergistically enhanced the targeted therapeutics against liver cancer via nanotechnology and immunotherapy, and it is expected to become a safe and multifunctional treatment platform in clinical oncology.

摘要

砷通过多种途径具有优异的抗晚期肝癌作用,但由于其严重的全身毒性,需要一种安全有效的递药策略。基于聚多巴胺(PDA)螯合金属离子的特性,将砷固定在有机载体上,并成功构建了一种类似 M1 型巨噬细胞膜(MM)伪装的锰砷配合物介孔聚多巴胺(MnAsOx@MP@M)纳米平台。在细胞水平上评估了 MnAsOx@MP@M 的肿瘤抑制和肿瘤定位作用,以及在 Hepa1-6 荷瘤小鼠模型中的抗肝癌作用。该纳米平台通过 MM 的天然归巢特性靶向肿瘤部位,在酸性环境中完全降解并释放药物以杀死肿瘤细胞,同时在促进肿瘤相关巨噬细胞(TAMs)重极化方面发挥免疫调节作用。MnAsOx@MP@M 通过纳米技术和免疫疗法协同增强了肝癌的靶向治疗效果,有望成为临床肿瘤学中安全多功能的治疗平台。

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