A hyaluronic acid-modified copper iron sulfide nanoplatform loaded with paclitaxel for synergistic chemotherapy/chemodynamic/photothermal cancer therapy.

In this study, a tumor targeting nanoplatform was designed and prepared for synergistic therapy of cancer. CuFeS2 (CFS) was synthesized as a nanocarrier and further modified with (3-aminopropyl) triethoxysilane (APTES) and methoxy polyethylene glycol-grafted hyaluronic acid (HA-mPEG). Paclitaxel (PTX) was then loaded to construct a multifunctional nanoplatform (PTX/CFS@APTES-HA-mPEG). Under NIR laser irradiation at 980 nm, the nanoplatform exhibited excellent photothermal performance. Moreover, PTX/CFS@APTES-HA-mPEG effectively generated cytotoxic hydroxyl radicals (•OH) via Fenton/Fenton-like reactions, thus enhancing the reactive oxygen species (ROS)-mediated therapeutic effect. The nanoplatform also exhibited NIR/GSH dual-responsive drug release behavior that enabled rapid and controlled PTX release at the tumor site. In vivo studies demonstrated the effective tumor inhibition efficacy of PTX/CFS@APTES-HA-mPEG. By integrating chemotherapy, chemodynamic therapy, and photothermal therapy, this platform not only overcame the limitations of monotherapy but also enhanced systemic stability, offering novel insights for synergistic tumor treatment.