Preparation of hierarchically targetable Astragalus polysaccharide lipid nanoparticles and study on their therapeutic effect on orthotopic colon cancer

An oral targeted drug delivery system based on polysaccharides can successfully target and deliver drugs to diseased sites in the colon, optimize therapeutic effects, and reduce adverse reactions. In this study, we developed a multifunctional, orally administered, colon-targeted, drug-loaded nanoparticles (SN38-SLN-APS NPs), based on Astragalus polysaccharides (APS), and loaded it with the anti-tumor drug 7-ethyl-10-hydroxycamptothecin (SN38). The surfaces of the SN38-SLN-APS NPs were modified using APS, APS undergoes almost no degradation in the stomach or small intestine, thereby protecting SN38-SLN-APS NPs and enabling its delivery into the colon. APS possess a negative charge, which can diminish the adsorption of mucoproteins and facilitate the translocation of SN38-SLN-APS NPs through the mucus layer. Upon reaching the colon, the SN38-SLN-APS NPs are destroyed by colonic bacteria. This approach enhances the gut microbiota in colon cancer by augmenting the amount and diversity of intestinal bacteria. We functionalized liposomes with the tumor-homing and -penetrating peptide iRGD; NPs treated with iRGD can augment drug accumulation at tumor locations while diminishing retention in normal tissues, hence producing anti-tumor effects. This study developed a colon-specific multifunctional NPs. They may accurately target the colon and attach to tumor cells, so successfully preventing the early absorption of medicines in the upper digestive system. SN38-SLN-APS NPs effectively safeguard the medicine against degradation by gastric acid and digestive enzymes, ensuring the active components reach the target site intact. This novel technique provides a new therapy avenue for colorectal cancer, anticipated to markedly improve therapeutic efficacy and diminish adverse effects.