An Active-Targeted ZIF8-Based Nanotheranostic Platform for Ultrasound Imaging-Guided Synergistic Therapy of Triple-Negative Breast Cancer

Purpose: To address the therapeutic challenges associated with triple-negative breast cancer (TNBC), we developed a folic acid-polyethylene glycol-modified ZIF8-based nanotheranostic platform (FA-PEG@ZIF8@CIP) designed to integrate synergistic sonodynamic therapy, chemotherapy, and immune activation for enhanced antitumor treatment. Methods: FA-PEG@ZIF8@CIP was constructed as a folic acid-polyethylene glycol-functionalized ZIF8 nanoplatform for the delivery of ciprofloxacin. In this system, ciprofloxacin acted as both a sonosensitizer and a chemotherapeutic agent, while the ZIF8 carrier provided pH-responsive release behavior in the acidic tumor microenvironment. The platform was further evaluated for its physicochemical properties, cellular uptake, antitumor efficacy, immune activation, and ultrasound imaging performance through a series of in vitro and in vivo experiments. Results: T cells in tumor tissues and spleen increased to 18.7% and 14.6%, respectively, corresponding to approximately 3.0-fold and 2.9-fold increases over the PBS group. The antitumor efficacy of FA-PEG@ZIF8@CIP+US was 4.21-fold higher than that of PBS. Moreover, the platform demonstrated effective ultrasound imaging capability, supporting its application for imaging-guided therapy. Collectively, these findings suggest that FA-PEG@ZIF8@CIP exerts therapeutic effects through the coordinated actions of sonodynamic therapy, chemotherapy, and immune modulation. Conclusion: This multifunctional nanosystem enables the integration of diagnosis and therapy and represents a promising strategy for TNBC treatment. By combining targeted delivery, pH-responsive drug release, ultrasound imaging, and synergistic therapeutic effects within a single platform, FA-PEG@ZIF8@CIP may offer a valuable approach for improving theranostic outcomes in TNBC.