Structural characterization and anticancer enhancement of selenized squid ink glycosaminoglycan nanoparticles

Squid ink polysaccharide 4 (SIP4), a marine-derived sulfated glycosaminoglycan with favorable biocompatibility and coordination capacity, was employed as a functional template and stabilizing matrix for the synthesis of selenized nanoparticles (SIP4-SeNPs). The optimal SIP4 concentration (0.4 mg/mL) yielded nanoparticles with the highest selenium incorporation (23.88%, ICP-MS), smallest particle size (130.57 nm), and a negative zeta potential (-24.23 mV). Spectroscopic and microscopic analyses (UV-Vis, FT-IR, SEM, DSC, TGA, XRD) confirmed selenium-induced structural reorganization and the formation of uniform, semi-crystalline SIP4-SeNPs stabilized by hydroxyl, carboxyl, and sulfate groups. The nanoparticles exhibited improved stability at 4 °C for up to 14 days. Biological evaluations showed that SIP4-SeNPs significantly enhanced antiproliferative activity against MDA-MB-231 cells with a markedly lower IC₅₀ than SIP4, while maintaining low cytotoxicity toward MCF-10 A cells. Apoptosis analysis and ROS detection indicated that SIP4-SeNPs promote cancer cell death through oxidative stress-mediated pathways. This study demonstrates that SIP4-based selenium nanoparticles are promising candidates for breast cancer therapy with improved efficacy and safety.