Enhancing chemoimmunotherapy for colorectal cancer with paclitaxel and alantolactone via CD44-Targeted nanoparticles: A STAT3 signaling pathway modulation approach

Enhancing chemoimmunotherapy for colorectal cancer with paclitaxel and alantolactone via CD44-Targeted nanoparticles: A STAT3 signaling pathway modulation approach

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Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making gruvi golden lager 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 fleshlight automatique 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.