Effect of different poloxamers on anti-cancer activities of targeting folic acid-fucoidan nanogels for multi-drug delivery.

Multi-drug delivery systems for co-administrating multiple therapeutic agents have attracted significant attention in anticancer therapy due to their ability to enhance synergistic effects, improve tumor targeting, and mitigate drug resistance and systemic toxicity. In this study, self-assembled folic acid-functionalized fucoidan-poloxamer nanogels were developed as potential platforms for the co-delivery of cisplatin (Cis) and curcumin (Cur) to investigate their synergistic therapeutic efficacy. Two types of poloxamers, P403 and P407, differing in the length of their PPO segments, were grafted onto fucoidan, followed by functionalization with the targeting ligand folic acid. The resulting nanogels (FA-Fud-P403 and FA-Fud-P407) were characterized through measurements of proton nuclear magnetic resonance spectrum (1H NMR), Fourier-transform infrared spectroscopy (FT-IR), and dynamic light scattering (DLS). Comapred to the FA-Fud-P407, FA-Fud-P403 had lower CMC value and smaller particle size, therefore improving the drug encapsulation efficacy. Meanwhile, the drug release studies revealed pH-responsive Fickian diffusion with an initial burst at acidic pH (5.5), followed by Korsmeyer-Peppas kinetics. Interestingly, the in vitro cell studies demonstrated that dual drug-loaded FA-Fud-P403 nanogels induced significantly higher cytotoxicity in MCF-7 breast cancer cells, while exhibiting reduced toxicity toward human dermal fibroblast cells (HDF) compared to FA-Fud-P407 and single drug-loaded formulations. Furthermore, in vivo evaluations in MCF-7 tumor-bearing mice confirmed the superior tumor inhibition with FA-Fud-P403@Cur/Cis, highlighting the potential of this dual drug delivery system to achieve synergistic therapeutic efficacy and minimize adverse effects associated with conventional chemotherapy.