A redox-responsive nanoparticle with RGD-targeted effect for photo-chemo therapy of triple-negative breast cancer

Abstract

Traditional chemotherapeutics for triple-negative breast cancer (TNBC) has a series of limitations, including low solubility, poor selectivity and severe side effects. To overcome these challenges, a redox-responsive polymeric nano-micelles RPSSD@IR780/DOC equipped with tumor-targeting RGD oligopeptide, and encapsulated chemotherapeutic agent docetaxel (DOC) and photosensitizer IR-780 iodide (IR780) was produced in the present study. This nanoparticle effectively improved the solubility of DOC and IR780 by 24.4-fold and 410-fold, respectively. By conjugating with the RGD oligopeptide, the selectivity and cellular uptake of DOC and IR780 in tumor cells was significantly enhanced. In tumors treated with RPSSD@IR780/DOC, high reductive microenvironment triggered breakage of disulfide bonds in the nanoparticles, thereby promoting DOC and IR780 release. IR780 generated large amounts of reactive oxygen species (ROS) and near-infrared (NIR) light-excited local heat, resulting in a synergistic anti-tumor effect. Following the treatment, the tumor suppression rate reached 92.74 %, and the survival time was extended to 50 days in mice. In addition, RPSSD@IR780/DOC had excellent biocompatibility and biosafety, significantly ameliorating systemic adverse effects associated with chemotherapeutic agents. In conclusion, RPSSD@IR780/DOC has a great potential as a novel redox-responsive and tumor-targeting nanodrug for photo-chemo therapy (PCT) in TNBC.