Chitosan functionalized with O-Phospho-L-Serine for enhanced DNA binding and physiological solubility

Year 2025, Issue: 063, 86 - 100, 30.12.2025

Kevser Bal

https://doi.org/10.59313/jsr-a.1768302

https://izlik.org/JA88NG38UX

Abstract

O-phospho-L-serine (OPLS) was successfully functionalized with chitosan in this study to create Chi-OPLS, a modified polymer that is more soluble and compatible with negatively charged biomolecules like plasmid DNA (pDNA). The goal of the functionalization strategy was to add new secondary amines and hydroxyl groups along the backbone of chitosan while preserving the majority of primary amine groups. This situation wasş0 aimed to improve interaction of polymer with pDNA, enabling efficient complexation in lower polymer concentrations. Chi-OPLS’ structure was analyzed by Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (1H NMR) spectroscopy. Dynamic light scattering (DLS) was used to optimize the physicochemical properties such as particle size, zeta potential, and polydispersity index of the nanoparticles at different Chi:TPP ratios. Optimized nanoparticles showed 110.5±5.52 nm for Z-average particle size and 0.12±0.02 for PDI. Zeta potential value is 22.05±2.05 mV. Importantly, according to raw chitosan, OPLS modification greatly increased solubility behaviour at physiological pH. In vitro cytotoxicity tests confirmed that modified nanoparticles have no cytotoxicity in HEK293T cells. Furthermore, pDNA binding capacity was significantly increased. This value decrease in the optimal complexation ratio from 5:1 in raw chitosan to 2:1 in Chi-OPLS. In summary, the Chi-OPLS system highlights its advanced physicochemical properties and is a suitable vehicle system for delivering nucleic acids and other anionic molecules.

Keywords

O-phospho-L-serine , Biocompatible nanocarriers , Chitosan-based nanoparticle systems , Chitosan functionalization

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