Protamine-modified CuAu nanocarrier enhances aptamer-mediated synergistic therapy for breast cancer.

Although aptamers held promise for precision cancer therapy, their physiological instability and the lack of multifunctional delivery platforms that enabled synergistic therapeutic effects remained key challenges. In this study, a nanocarrier based on protamine-modified CuAu bimetallic nanozyme was constructed to co-load AT11 aptamer and Doxorubicin (Dox), named BPAD. In this system, the AT11 aptamer was adsorbed onto the surface of the positively charged nanocarrier via electrostatic interactions, which reversed the surface charge and formed a dense targeting shell, thereby significantly enhancing aptamer stability to ensure effective targeting. Notably, BPAD integrated enzyme-like activity, photothermal conversion, glutathione (GSH) depletion, and drug delivery capabilities, aiming to destroy the normal physiological functions of cancer cells through multiple combined therapeutic mechanisms to enhance treatment efficacy. Preliminary in vitro experiments demonstrated that BPAD was efficiently internalized by cancer cells and exhibited potent cytotoxicity against cancer cells, providing a stable delivery strategy in aptamer-mediated targeted therapy.