Anticancer therapeutic potential of phosphorylated galactosylated chitosan against N-nitrosodiethyl amine-induced hepatocarcinogenesis

Chitosan is a natural polyfunctional polymer that can be modified to achieve compounds with tailored properties for targeting and treating different cancers. In this study, we report the development and anticancer potential of phosphorylated galactosylated chitosan (PGC). The synthesized compound was characterized by FT-IR, NMR, and mass spectroscopy. The interaction of PGC with asialoglycoprotein receptors (ASGPR) and cellular internalization in HepG2 cells was studied using in silico and uptake studies respectively. PGC was evaluated for its metal chelating, ferric ion reducing, superoxide, and lipid peroxide (LPO) inhibiting potential. Further, anticancer therapeutic potential of PGC was evaluated against N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in a mice model. After development of cancer, PGC was administered to the treatment group (0.5 mg/kg bw, intravenously), once a week for 4 weeks. Characterization studies of PGC revealed successful phosphorylation and galactosylation of chitosan. A strong interaction of PGC with ASGP-receptors was predicted by computational studies and cellular internalization studies demonstrated 98.76 ± 0.53% uptake of PGC in the HepG2 cells. A good metal chelating, ferric ion reducing, and free radical scavenging activity was demonstrated by PGC. The anticancer therapeutic potential of PGC was evident from the observation that PGC treatment increased number of tumor free animals (50%) (6/12) and significantly (p ≤ 0.05) lowered tumor multiplicity as compared to untreated tumor group. Phosphorylated galactosylated chitosan synthesis and its antitumor effect: Phosphorylated galactosylated chitosan (PGC) was synthesized to impart anticancer capabilities to the chitosan. The successful conjugation of the groups was confirmed by characterizing PGC using FT-IR, NMR, and LC-Mass spectroscopy. PGC demonstrated strong interactions with asialoglycoprotein receptors and showed higher uptake in HepG2 cells as compared to the unmodified chitosan. PGC exhibited good in vitro/in vivo antioxidant properties, metal chelating ability, and ferric ion reducing ability. PGC was biocompatible and showed no signs of in vivo toxicity. Further, it displayed strong anticancer therapeutic potential against hepatocellular carcinoma. [Display omitted] •PGC exhibited strong interaction with asialoglycoprotein receptor.•Modification of chitosan improved the in vitro antioxidant property.•PGC was biocompatible and exhibited no toxicity.