Co-delivery paclitaxel and IR783 as nanoparticles for potentiated chemo-photothermal-immunotherapy of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is highly malignant and invasive, which is the major challenge of breast cancer treatment. Although chemo-immunotherapy is currently the most promising treatment option, its efficacy in treating TNBC is limited due to challenges such as low immune response rate and severe side effects. In this study, a nanocarrier PEI-GCP(Z)/mPEG with excellent water solubility and high drug-loading capacity was designed, and it was used to load the paclitaxel (PTX) and photosensitizer IR783 to prepare nanoparticles PEI-GCP(Z)/mPEG@PTX@IR783 (PPI). The PPI demonstrated high loading efficiency for PTX and IR783, enabling the chemotherapy effect of PTX and the photothermal therapy under 808 nm laser irradiation, that combined chemotherapy and photothermal therapy. Furthermore, PPI could induce immunogenic cell death (ICD), promote dendritic cells (DCs) maturation, and increase the infiltration of cytotoxic T lymphocytes (CTLs) in the tumor site, thereby enhancing anti-tumor immunity. PPI also increased the proportion of effector memory T cells (Tem), thereby supporting long-term anti-tumor immunity. Both <i>in vitro</i> and <i>in vivo</i> studies demonstrated that PPI effectively targets tumor cells and significantly inhibits tumor growth through the combined effects of chemo-photothermal-immunotherapy. Therefore, PPI is a promising nanoparticle with multi-modal therapeutic effects, offering substantial potential for the treatment of TNBC.