Development and Characterization of Folic Acid‐Decorated Fucoidan‐Poloxamer 407 Self‐Assembled Nanogels Co‐Loading Curcumin and Paclitaxel for Synergistically Enhanced Chemotherapeutic Efficacy

ABSTRACT Cancer‐targeted nanomedicines demonstrate considerable potential in anticancer treatment due to their unique properties that improve therapeutic efficiency while minimizing off‐target effects. In this research, curcumin (Cur) and paclitaxel (PTX) were co‐loaded into dual‐targeting folate receptor/P‐selectin nanocarriers, which were based on folate‐conjugated fucoidan‐poloxamer 407 copolymers (FA‐FP407), aiming to inhibit breast cancer through intravenous administration. The successful synthesis of the self‐assembled nanogels was confirmed by analyzing their chemical composition. The resulting nanogels exhibited optimal physicochemical properties, including a negative surface charge, spherical morphology, and a hydrodynamic diameter of 158.27 ± 3.15 nm, along with high drug‐loading efficiency. The in vitro drug release from the nanogels significantly accelerated within the tumor microenvironment at pH 5.5, while it slowed down under physiological conditions. The drug release kinetics adhered to a Fickian diffusion model. Additionally, the blank nanocarriers were both hemocompatible and cytocompatible, although they exhibited slight growth inhibition of MCF‐7 breast cancer cells. FA‐FP407@Cur@PTX demonstrated a lower IC 50 compared to both free drug formulations and single drug‐loaded nanogels in MCF‐7 cells, indicating that FA‐FP407@Cur@PTX nanogels could enhance anticancer activity by co‐administering different drugs and precisely accumulating drugs at the cancerous site. This effect is attributed to strong synergistic actions and receptor‐mediated cellular uptake. This study provides a solid foundation for advancing targeted nanomedicine, facilitating the co‐delivery of multiple therapeutic agents to achieve superior synergistic effects in chemotherapy.