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.