摘要Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death(ICD),making it a promising strategy for clinical application.Alantolactone(A)was found to augment the anticancer efficacy of paclitaxel(P)at a molar ratio of 1:0.5(P:A)through induction of more potent ICD via modulation of STAT3 signaling pathways.Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents,thereby enhancing multi-drug chemoimmunotherapy.To improve tumor targeting ability and bioavailability of hydrophobic drugs,an amphiphilic prodrug conjugate(HA-PTX)was chemically modified with paclitaxel(PTX)and hyaluronic acid(HA)as a backbone.Based on this concept,CD44-targeted nanodrugs(A@HAP NPs)were developed for co-delivery of A and P in colorectal cancer treatment,aiming to achieve synergistic toxicity-based chemo-immunotherapy.The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting,providing a solid foundation for subsequent synergistic therapy and immunoregulation.In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation,thus offering a novel approach for colorectal cancer chemoimmunotherapy.