Galactosylated Chitosan Oligosaccharide Nanoparticles for Hepatocellular Carcinoma Cell-Targeted Delivery of Adenosine Triphosphate

Abstract

Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were 51.03 ± 3.26 nm and 30.50 ± 1.25 mV, respectively, suggesting suitable properties for a drug delivery system. Subsequently, the cytotoxicity of Gal-CSO/ATP nanoparticles were examined by the methyl tetrazolium (MTT) assay, and the half maximal inhibitory concentration (IC50) values were calculated with HepG2 (human hepatocellular carcinoma cell line) cells. The results showed that the cytotoxic effect of nanoparticles on HepG2 cells was low. In the meantime, it was also found that the Gal-CSO/ATP nanoparticles could be uptaken by HepG2 cells, due to expression of the asialoglycoprotein receptor (ASGP-R) on their surfaces. The presented results indicate that the Gal-CSO nanoparticles might be very attractive to be used as an intracellular drug delivery carrier for hepatocellular carcinoma cell targeting, thus warranting further in vivo or clinical investigations.

Anticancer and Anti-Inflammatory Properties of Chitin and Chitosan Oligosaccharides

“…In addition, CSOAA showed negligible cytotoxicity in the human head and neck cancer cell line, FaDu and cellular uptake of DOX was higher in the nanoparticle-treated cells in comparison with free DOX-treated cells. Zhu et al have evaluated the characteristics of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) (Gal-CSO/ATP) nanoparticles [ 19 ]. They estimated the cytotoxicity of Gal-CSO/ATP nanoparticles in HepG2 cells by using methyl tetrazolium (MTT) assay, and calculated the half maximal inhibitory concentration (IC 50 ) values.…”

In Vitro Anticancer Activity of 5’ Fluo Uracil Coated Chitosan Nanoparticle

“…2) the 5FCN was low compared to the chitosan oligosaccharide loaded with ATP (154.8µg/ml) against Hep G2 cell lines [8]. Elkholi et al [3] used trimethyl chitosan nanoparticles against Hep G2 cell lines and its IC50 value was fivefold increased in concentration compared to the IC50 of the present study.…”

Nanomedicine in management of hepatocellular carcinoma: Challenges and opportunities

“…For example, 5‐fluorouracil‐loaded galactosylated chitosan NPs resulted in extensive accumulation of the drug at tumor tissues, as compared with other healthy tissues, with 8.69‐, 23.35‐, 79.96‐ and 85.15‐fold increase in accumulation when compared to normal liver tissue, kidney, heart and blood, respectively. Furthermore, greater tumor inhibition was demonstrated when these NPs were tested on orthotropic mice models against the free drug, suggesting capability of targeted NPs to improve therapeutic efficacy by improving biodistribution profile of the encapsulated drug . ATP can bind to P2 receptors, a type of purinergic receptor that is expressed on cancer cells.…”