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

<b>Aim:</b> 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. <b>Methods:</b> 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 <i>in vivo</i> for its anti-liver cancer effect in a Hepa1-6 tumor-bearing mouse model. <b>Results:</b> 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. <b>Conclusion:</b> 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. Small inorganic molecules drug was assembled on an organic carrier. Arsenic was combined with metallic hydroxyl (Mn-OH) groups by adsorption to form a monodentate compound. The metal ion chelating property of polydopamine was utilized to load manganese. The mesoporous structure of polydopamine was favorable for loading more metal ions. polydopamine was completely degraded in an acidic environment, and the product dopamine could regulate tumor vascular homeostasis. The camouflage of the macrophage cell membrane helped the nano-drug delivery system evade immune surveillance, prolong circulation time in the body and enrich the tumor. The tumor sphere experiment preliminarily confirmed that the enhanced tumor permeability of the preparation was based on macrophage cell membrane. M1 macrophage membrane helped regulate the TAMs immune promotion.

**研究目的**：砷可通过多条通路发挥优异的抗晚期肝癌活性，但其严重的全身毒性亟需开发安全高效的递送策略。
**研究方法**：基于聚多巴胺（polydopamine, PDA）的金属离子螯合特性，将砷固定于有机载体之上，成功构建了经M1样巨噬细胞膜（M1-like macrophage cell membrane, MM）伪装的锰-砷复合介孔聚多巴胺纳米平台（MnAsOx@MP@M）。通过细胞水平实验评估了MnAsOx@MP@M的肿瘤抑制能力与肿瘤定位特性，并在Hepa1-6荷瘤小鼠模型中开展体内抗肝癌药效评价。
**研究结果**：该纳米平台借助MM的天然归巢特性靶向肿瘤部位，在酸性微环境中完全降解并释放药物以杀伤肿瘤细胞，同时发挥免疫调节作用，促进肿瘤相关巨噬细胞（tumor-associated macrophages, TAMs）的复极化。
**研究结论**：MnAsOx@MP@M通过纳米技术与免疫疗法协同增强了肝癌靶向治疗效果，有望成为临床肿瘤学领域安全且多功能的治疗平台。
将小分子无机药物组装于有机载体：砷通过吸附作用与金属羟基（Mn-OH）基团结合形成单齿配位化合物；利用聚多巴胺的金属离子螯合特性负载锰离子，其介孔结构可负载更多金属离子。聚多巴胺可在酸性环境中完全降解，其降解产物多巴胺能够调节肿瘤血管稳态。巨噬细胞膜伪装可帮助纳米给药系统逃避免疫监视、延长体内循环时间并富集于肿瘤组织。肿瘤球实验初步证实，该制剂增强的肿瘤穿透性依赖于巨噬细胞膜；M1巨噬细胞膜可调控TAMs的免疫促进功能。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于一种新型膜伪装仿生纳米平台（MnAsOx@MP@M），该平台通过结合砷复合物和M1样巨噬细胞膜，实现了对肝癌的靶向治疗和免疫调节。研究展示了该平台在酸性环境中完全降解并释放药物以杀死肿瘤细胞的能力，同时促进肿瘤相关巨噬细胞的重新极化，为肝癌治疗提供了安全有效的多功能治疗策略。