Self-Signal-Triggered Drug Delivery System for Tumor Therapy Using Cancer Cell Membrane-Coated Biocompatible Mn3O4 Nanocomposites.

Abstract

In anti-cancer metastasis treatment, precise drug delivery to cancer cells remains a challenge. Innovative nanocomposites are developed to tackle these issues effectively. The approach involves the creation of manganese oxide (Mn3O4) nanoparticles (NPs) and their functionalization using trisodium citrate to yield functionalized Mn3O4 NPs (F-Mn3O4 NPs), with enhanced water solubility, stability, and biocompatibility. Subsequently, the chemotherapeutic drug doxorubicin (DOX) is encapsulated with Mn3O4 NPs, resulting in DOX/Mn3O4 NPs. To achieve cell-specific targeting, These NPs are coated with HeLa cell membranes (HCM), forming HCM/DOX/Mn3O4. For further refinement, a transferrin (Tf) receptor is integrated with cracked HCM to create Tf-HCM/DOX/Mn3O4 nanocomposites (NC) with specific cell membrane targeting capabilities. The resulting Tf-HCM/DOX/Mn3O4 NC exhibits excellent drug encapsulation efficiency (97.5%) and displays triggered drug release when exposed to NIR laser irradiation in the tumor's environment (pH 5.0 and 6.5). Furthermore, these nanocomposites show resistance to macrophage uptake and demonstrate homotypic cancer cell targeting specificity, even in the presence of other tumor cells. In vitro toxicity tests show that Tf-HCM/DOX/Mn3O4 NC achieves significant anticancer activity against HeLa and BT20 cancer cells, with percentages of 76.46% and 71.36%, respectively. These results indicate the potential of Tf-HCM/DOX/Mn3O4 NC as an effective nanoplatform for chemo-photothermal therapy.