Preparation of baicalin nano prodrug and its effect on inhibiting metastasis of triple-negative breast cancer

Background Triple-negative breast cancer (TNBC) faces great challenges in clinical treatment, owing to the lack of specific therapeutic targets and easy metastasis. The natural component baicalin can effectively inhibit the growth and metastasis of TNBC; however, it has some limitations, such as poor targeting and side effects. Nano targeted delivery systems can improve drug efficacy by enhancing drug accumulation and controlling drug release. Objective Trop-2 transmembrane glycoprotein expression is high in TNBC cells, suggesting that it can serve as a specific active targeting molecular-modified nano drug delivery system for TNBC to overcome non-specific distribution. Based on the characteristics of high-concentration glutathione in the tumor microenvironment, redox-sensitive nano-prodrugs (Trop2-BA-ss-PPEP) have been designed to achieve intelligent slow control and release of drugs. Methods The chemical structure of the Trop2-BA-ss-PPEP, and its stability, reductive response to drug release behavior, and targeting ability in vitro were characterized. Cell experiments and a transplanted tumor model verified the anti-tumor effect and biosafety. Results Trop2-BA-ss-PPEP was stable in a physiological environment and rapidly released the drug under reducing conditions. The experiments showed that Trop2-BA-ss-PPEP significantly promoted cellular uptake, and drug accumulation and maintenance time at the tumor site were increased. It enhanced the inhibitory effect on metastasis in vivo and in vitro, and no obvious toxicity or side effects were observed. Conclusion Trop2-BA-ss-PPEP was successfully constructed. The targeting ability, microenvironment responsiveness, and anti-tumor metastatic effects of Trop2-BA-ss-PPEP provide a new strategy for TNBC therapy, which has good application and transformation potential.