α-lipoic acid and L-serine conjugated chitosan as a stimuli-responsive drug delivery platform

In this study, a novel chitosan-based nanocarrier system was developed through dual modification with α-lipoic acid and l-serine (Chi_Lipo-Ser) to enhance its physicochemical and biological properties for drug delivery applications. FTIR and ¹H NMR spectroscopy verified the successful conjugation of functional groups onto the chitosan backbone, while GPC analysis confirmed an increase in molecular weight consistent with the modification. Compared with native chitosan, the Chi_Lipo-Ser exhibited improved solubility at physiological pH and enhanced buffering capacity. Nanoparticles prepared via ionotropic gelation demonstrated favorable characteristics, including an average particle size of ∼150 nm, low polydispersity, and a positive surface charge. Redox sensitivity was evidenced by DLS analysis, which revealed particle destabilization in the presence of 10-20 mM DTT, resulting from disulfide bond cleavage. Importantly, Chi_Lipo-Ser modification significantly enhanced the encapsulation efficiency of curcumin compared to unmodified chitosan, while the resulting formulations also exhibited effective release behavior at pH 5, mimicking the tumor intracellular environment. Furthermore, in vitro cytotoxicity assays showed that CUR-loaded Chi_Lipo-Ser nanoparticles exerted cytotoxic effects against HeLa and HT29 cancer cells while maintaining acceptable biocompatibility in BJ fibroblasts. Collectively, these results highlight the potential of Chi_Lipo-Ser nanoparticles as a promising platform for stimuli-responsive anticancer drug delivery.