M1 macrophage membrane-coated nickel-arsenic nanocomplex promoting synergistic treatment of hepatocellular carcinoma.

Abstract

By inducing apoptosis, promoting differentiation and reducing the migration of cancer cells, arsenic has a higher therapeutic effect and lower risk of recurrence and metastasis than conventional anticancer drugs. However, the low bioavailability and adverse side effects of arsenic hinder its application in hepatocellular carcinoma (HCC). Therefore, a M1 macrophage membrane-coated nickel-arsenic/polydopamine nanocomplex (NiAsOx@P@M) was constructed to enhance the combined antitumor effects of chemotherapy and immunotherapy. The nanocomplex consisted of a nickel-arsenic oxide core, a polydopamine (PDA) shell and a M1 macrophage membrane (MM) coating. MM endowed the nanocomplex with natural tumor homing and immune escape properties, and the nanocomplex was gradually accumulated in the tumor tissue during the internal circulation. The acid response of PDA led to its degradation in the tumor microenvironment (TME). The degradation product dopamine (DA) and MM jointly promoted tumor immunity and regulated tumor-associated macrophages (TAMs) to repolarization M1 phenotype. The nickel-arsenic oxide core dissociated in an acid environment and released arsenic, thus killing tumor cells. In summary, the nanocomplex provided a promising delivery strategy for arsenic therapy of HCC and a novel design idea for the conversion of inorganic drugs into organic preparations.