Preparation and property study of self-assembled nanoparticles from thiolated fucoidan and doxorubicin

In cancer therapy, addressing the tumor microenvironment remains a critical challenge. This study presented a novel drug delivery system based on thiolated fucoidan (FUC-SH), a marine-derived polysaccharide possessing immunomodulatory properties. FUC-SH was synthesized via cysteine conjugation and self-assembled with doxorubicin (DOX) to form stable nanoparticles through electrostatic interactions and disulfide crosslinking. These nanoparticles exhibited pH/GSH dual-responsive drug release properties, enabling selective drug release in tumor microenvironments. Characterization revealed an average particle size of 141.62 ± 16.94 nm, a Zeta potential of -23.1 ± 2.67 mV, and a high drug-loading efficiency (70.97 ± 1.70 %). Cellular assays demonstrated enhanced tumor-targeted cytotoxicity and immune-stimulating effects, including elevated ROS and cytokine production in RAW 264.7 macrophages. This study focused on in vitro evaluations and the findings highlighted the potential of FUC-SH/DOX nanoparticles as a multifunctional platform for tumor-targeted therapy, while the future studies planned to explore in vivo efficacy.