Homologous Tumor Cell-Derived Biomimetic Nano-Trojan Horse Integrating Chemotherapy with Genetherapy for Boosting Triple-Negative Breast Cancer Therapy

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that carries the worst prognosis and lacks specific therapeutic targets. To achieve accurate “cargos” delivery at the TNBC site, we herein constructed a novel biomimetic nano-Trojan horse integrating chemotherapy with gene therapy for boosting TNBC treatment. Briefly, we initially introduce the diselenide-bond-containing organosilica moieties into the framework of mesoporous silica nanoparticles (MONs), thereby conferring biodegradability to intratumoral redox conditions in the obtained MON_Se. Subsequently, doxorubicin (Dox) and therapeutic miR-34a are loaded into MON_Se, thus achieving the combination of chemotherapy and gene-therapy. After homologous tumor cell membrane coating, the ultimate homologous tumor cell-derived biomimetic nano-Trojan horse (namely, MON_Se@Dox@miR-34a@CM) can selectively enter the tumor cells in a stealth-like fashion. Notably, such a nanoplatform not only synergistically eradicated the tumor but also inhibited the proliferation of breast cancer stem-like cells (BCSCs) in vitro and in vivo. With the integration of homologous tumor cell membrane-facilitated intratumoral accumulation, excellent biodegradability, and synergistic gene-chemotherapy, our biomimetic nanocarriers hold tremendous promise for the cure of TNBC in the future.