Chondroitin sulfate modification enhances the targeting and therapeutic effect of nanomedicine on AOM/DSS-induced mouse colon cancer

Abstract

In this study, under the guidance of chitosan, chondroitin sulfate (CS)-modified PLGA nanoparticles were used to load the antitumor drug 10-Hydroxy camptothecin (HCPT), and the obtained HCPT/CS-CN-PLGA NP was successfully characterized. In the drug release experiment, it was revealed that the drug-loaded nanoparticles can be stably maintained in an acidic environment and structurally destroyed under neutral conditions to rapidly release the drug. In in vitro flow cytometry experiments, CS-modified nanoparticles not only can enter cells more, but also promote HCPT to inhibit the action of topoisomerase Ⅰ, thereby promoting cell apoptosis. The MTT experiment also confirmed this effect. In the colon cancer experiment induced by AOM/DSS, HCPT/CS-CN-PLGA NP showed more excellent anti-tumor effect, not only able to maintain the body weight of mice, but also reduce the tumor nodules in mouse colon cancer. Laser confocal fluorescence microscopy showed that CS-CN-PLGA NP could be better aggregated in colon tumors, which also indicated its good tumor enrichment. The above results indicate that CS, as a ligand for CD44, can be used as a good nanomedicine targeting unit for the treatment of tumor disease models with high CD44 expression.