Thermosensitive spray-gel oxaliplatin delivery system for antitumor efficacy and mechanistic study in a mouse...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Postoperative recurrence of colorectal cancer is a significant clinical challenge.
• Residual tumor cells and an immunosuppressive tumor microenvironment contribute to poor patient prognosis.

Purpose of the Study:

• To develop a thermosensitive, in situ sprayable gel (iSGel@OXA) for localized postoperative delivery of oxaliplatin (OXA).
• To evaluate the efficacy and underlying mechanisms of iSGel@OXA in suppressing colorectal cancer regrowth and improving survival.

Main Methods:

• Development and characterization of a thermosensitive, in situ sprayable hydrogel for sustained oxaliplatin release.
• Evaluation of iSGel@OXA in a mouse model of incomplete colorectal cancer resection.
• Mechanistic investigations involving immune cell profiling, cytokine analysis, and pathway analysis (e.g., TGF-β, Stat1-Src).

Main Results:

• iSGel@OXA demonstrated excellent sprayability, rapid gelation, tissue adhesion, and sustained drug release.
• The treatment significantly suppressed tumor regrowth and prolonged survival in the mouse model.
• Mechanisms included synergistic regulation of CD4+ T cells and myeloid-derived suppressor cells, TNF-α upregulation, TGF-β pathway inhibition, promotion of apoptosis and immunogenic cell death (ICD).

Conclusions:

• Thermosensitive hydrogel-mediated local chemotherapy-immunotherapy offers a promising strategy for postoperative colorectal cancer treatment.
• iSGel@OXA effectively remodels the tumor microenvironment and enhances anti-tumor immunity.
• This approach provides a strong foundation for clinical translation in managing colorectal cancer recurrence.