Hyaluronic acid-functionalized nanoparticles enable enhanced chemo/chemodynamic therapy for the targeted treatment of colon cancer.

Colon cancer (CC) is the third most common cancer globally and one of the leading causes of death. Therefore, there is an urgent need to develop an efficient and low-toxicity CC treatment regimen. The combination of chemotherapy (CT) and chemodynamic therapy (CDT) has great potential in cancer treatment. In this work, an amphiphilic molecule, HA-Fc-PEG-SS-CPT, containing ferrocene and camptothecin (CPT) was designed and synthesized. HA-Fc-PEG-SS-CPT was self-assembled and loaded with doxorubicin (DOX) to prepare a nanoparticle (HCF@DOX) with active targeting, GSH consumption, controlled drug release, and induction of reactive oxygen species (ROS) burst to achieve CT/CDT anti-CC. The results of in vitro and in vivo studies demonstrated that the particle size and morphology of HCF@DOX are suitable for passive targeting effects. HCF@DOX was found to have excellent stability, antitumor activity and biosafety. In addition, HCF@DOX achieved CT/CDT anti-CC by inhibiting tumour cell proliferation through ferroptosis and apoptosis. In summary, this study provides an interesting strategy for nanoparticles based on CT/CDT to enhance anti-CC efficacy. This research may pave the way for the development of innovative and transformative treatments for CC.