biostudies-literatureLiu DNational Natural Science Foundation of China330https://www.ebi.ac.uk/biostudies/studies/S-EPMC12751668biostudies-literatureUnknown44(1)Hepatocellular carcinoma (HCC), often arising from liver fibrosis in nonalcoholic fatty liver disease (NAFLD), remains a leading cause of cancer-related death. Targeting the gut-liver axis offers new therapeutic opportunities to prevent this progression. In this study, colon-targeted chitosan/pectin-based nanoparticles loaded with Astragalus polysaccharide (APs-CS/PT-NPs) were developed to modulate gut microbiota and inhibit liver tumorigenesis. The nanoparticles exhibited robust physicochemical stability and pH-responsive release. In vivo, oral administration of APs-CS/PT-NPs attenuated hepatic steatosis, reduced inflammatory cytokines, and suppressed NAFLD-induced HCC development. 16 S rRNA sequencing revealed restoration of microbial diversity and enhanced production of short-chain fattJournal of experimental & clinical cancer research : CRColon-Targeted astragalus polysaccharide nanoparticles prevent NAFLD-Driven hepatocarcinogenesis via microbiota remodeling and NF-κB Inhibition.PMC12751668No. 81704054Liang YLi RLiu DWang ZSun YLi MGe PfalseColon-Targeted astragalus polysaccharide nanoparticles prevent NAFLD-Driven hepatocarcinogenesis via microbiota remodeling and NF-κB Inhibition.Hepatocellular carcinoma (HCC), often arising from liver fibrosis in nonalcoholic fatty liver disease (NAFLD), remains a leading cause of cancer-related death. Targeting the gut-liver axis offers new therapeutic opportunities to prevent this progression. In this study, colon-targeted chitosan/pectin-based nanoparticles loaded with Astragalus polysaccharide (APs-CS/PT-NPs) were developed to modulate gut microbiota and inhibit liver tumorigenesis. The nanoparticles exhibited robust physicochemical stability and pH-responsive release. In vivo, oral administration of APs-CS/PT-NPs attenuated hepatic steatosis, reduced inflammatory cytokines, and suppressed NAFLD-induced HCC development. 16 S rRNA sequencing revealed restoration of microbial diversity and enhanced production of short-chain fatt2025-01-01T00:00:00Z2025 Dec2026-07-15T13:25:14.497Z2026-07-05T03:08:30.359ZS-EPMC127516684142224610.1186/s13046-025-03608-z