Cryo-Shocked Cancer Cell Biomimetic Carriers Enhance Tumor-Targeted Doxorubicin Delivery in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype with no defined therapeutic targets and high intratumoral heterogeneity. These features severely limit the efficacy of conventional chemotherapy. In this study, a biomimetic drug delivery platform was developed by cryo-shock treatment of 4T1 tumor cells (CS cells) to generate nonviable, structurally intact carriers, which were subsequently loaded with doxorubicin (DOX/CS cells). DOX/CS cells preserve native membrane proteins and chemotactic properties, facilitating enhanced tumor homing and tissue penetration without the risks associated with live-cell vectors. In vitro and in vivo analyses demonstrated that DOX/CS cells exhibit improved tumor-specific uptake, sustained drug release, and markedly enhanced antitumor activity compared to free DOX. Furthermore, systemic administration of DOX/CS cells achieved favorable biodistribution with minimal off-target toxicity. These findings indicate that cryo-shocked cancer cells offer a simplified yet potent platform for targeted drug delivery, offering a promising strategy for the safe and effective treatment of TNBC.