Membrane-coated BLM gene silencing plasmids and doxorubicin nanoparticles targeted for synergistic inhibition of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by its aggressive nature and limited options for targeted therapy, as well as a propensity for resistance to chemotherapy, primarily due to the absence of specific hormone receptors. The BLM DNA helicase protein is overexpressed in breast cancer tissues and is negatively correlated with patient survival outcomes. In the present study, we developed and synthesized PLGA nanoparticles (shBLM/DOX-NPs) that coencapsulate a plasmid encoding short hairpin RNA (shBLM) that targets the BLM gene alongside the chemotherapeutic agent doxorubicin (DOX). By utilizing the "homologous targeting" capability of the MDA-MB-231 cell membrane, these nanoparticles were camouflaged to facilitate targeted delivery to TNBC tumor sites. In vitro experiments demonstrated that shBLM/DOX-NPs@231 significantly diminished the expression of the BLM DNA helicase protein in TNBC cells and enhanced the inhibitory effects of DOX on the proliferation of TNBC tumor cells. Furthermore, in vivo studies confirmed that shBLM/DOX-NPs@231 effectively targeted therapy, thereby improving the efficacy of chemotherapy while exhibiting favorable biosafety profiles. Consequently, this nanodelivery system, which integrates gene therapy with chemotherapeutic agents, presents a promising and safe approach for the treatment of TNBC.