Biomimetic tumor cell membrane-coated nanomaterials combine gene therapy by Crispr/Cas9 and photothermal therapy in triple-negative breast cancer

To explore potential therapeutic strategies for triple-negative breast cancer (TNBC) and investigate targeted CDK9 inhibitors with reduced toxicity, a CRISPR/Cas9-based bionic tumor cell membrane-encapsulated nanocomposite was developed. The system primarily consists of mesoporous polydopamine, Cas9/gRNA, and the outer layer of TNBC cell membranes. It not only enables controlled release of Cas9/gRNA to suppress CDK9 expression but also synergistically induces apoptosis through photothermal effects. This nanocomposite exhibits excellent biocompatibility and demonstrates outstanding synergistic therapeutic effects. 808 nm irradiation triggers the release of Cas9/gRNA that inhibits CDK9, while simultaneously generating photothermal effects. This induces downregulation of Mcl-1 and cleavage of Caspase3, promoting tumor cell apoptosis, thereby achieving potent antitumor efficacy. This approach offers a promising strategy for targeting CDK9 in the treatment of triple-negative breast cancer.