Fe3O4-graphene oxide nanocomposites functionalized with hyaluronic acid and folic acid as dual pH/NIR-responsive platforms for synergistic chemophotothermal therapy of breast cancer

Abstract

Chemotherapy consistently exhibits constrained therapeutic efficacy due to inadequate tumor specificity and unavoidable multidrug resistance. However, the development of nanoscale drug carrier systems offers a promising therapeutic approach for cancer treatment, given their proven potential in targeted delivery and synergistic therapeutic outcomes. In this work, nanoparticles (NPs) designed for drug delivery and photothermal therapy (PTT) were fabricated by grafting hyaluronic acid (HA) and folic acid (FA) onto the surface of Fe₃O₄-modified graphene oxide (MGO). These MGO-HA-FA NPs demonstrated specific dual-targeting functionality for both CD44 and folate receptors. Meanwhile, the antitumor drug doxorubicin hydrochloride (DOX) was efficiently encapsulated by MGO-HA-FA and the drug loading capacity (DLC) could reach 58 wt%. And MGO-HA-FA demonstrated favorable biocompatibility, low systemic toxicity, and high photothermal conversion efficiency. Furthermore, upon near-infrared radiation (NIR) laser irradiation, DOX/MGO-HA-FA nanoparticles could in situ ablate tumor cells and further trigger drug release. This process demonstrated a remarkable synergistic therapeutic efficacy combining photothermal therapy and chemotherapy, achieving a tumor inhibition rate > 90%. When synergistically combined with photothermal therapy, this nanocomposite exhibits significantly enhanced antitumor efficacy against 4T1 tumor-bearing murine models relative to monotherapeutic approaches. This improvement is attributable primarily to its precisely controlled, tumor-targeted drug release mechanism and significantly reduced systemic toxicity. Thus, this study proposed a novel active dual-targeted chemophotothermal therapy (CPT) nanocarrier for targeted cancer therapy.