Homologous Tumor\nCell-Derived Biomimetic Nano-Trojan\nHorse Integrating Chemotherapy with Genetherapy for Boosting Triple-Negative\nBreast Cancer Therapy

Triple-negative breast cancer (TNBC) is a subtype of\nbreast cancer\nthat carries the worst prognosis and lacks specific therapeutic targets.\nTo achieve accurate “cargos” delivery at the TNBC site,\nwe herein constructed a novel biomimetic nano-Trojan horse integrating\nchemotherapy with gene therapy for boosting TNBC treatment. Briefly,\nwe initially introduce the diselenide-bond-containing organosilica\nmoieties into the framework of mesoporous silica nanoparticles (MONs),\nthereby conferring biodegradability to intratumoral redox conditions\nin the obtained MON<sub>Se</sub>. Subsequently, doxorubicin (Dox)\nand therapeutic miR-34a are loaded into MON<sub>Se</sub>, thus achieving\nthe combination of chemotherapy and gene-therapy. After homologous\ntumor cell membrane coating, the ultimate homologous tumor cell-derived\nbiomimetic nano-Trojan horse (namely, MON<sub>Se</sub>@Dox@miR-34a@CM)\ncan selectively enter the tumor cells in a stealth-like fashion. Notably,\nsuch a nanoplatform not only synergistically eradicated the tumor\nbut also inhibited the proliferation of breast cancer stem-like cells\n(BCSCs) <i>in vitro</i> and <i>in vivo</i>. With\nthe integration of homologous tumor cell membrane-facilitated intratumoral\naccumulation, excellent biodegradability, and synergistic gene-chemotherapy,\nour biomimetic nanocarriers hold tremendous promise for the cure of\nTNBC in the future.