Inulin-Based Nanoparticle Modulates Gut Microbiota and Immune Microenvironment for Improving Colorectal Cancer Therapy

In consideration of the important influence of gut microbiota on colorectal cancer (CRC) development and host immune system, regulating microbiota and intestinal environment can be an assisting approach to CRC treatment. To remodel tumor microenvironment, the anti-CRC molecular targeting drug regorafenib (REG)-encapsulating nanoparticle (UIRN) is constructed with the amphiphilic inulin-ursodeoxycholic acid conjugate. UIRN increases the intra-tumoral concentration and accumulation time of REG. In the CT26 tumor-bearing mouse model, the relative abundance of probiotics and short-chain fatty acid concentrations in colon are upregulated after treatment with UIRN, with decreased proportion of pro-tumoral bacteria. Combining gut microbiota modulation and the function of REG to induce polarization of tumor-associated macrophages toward the M1-type, UIRN conquers immunosuppression and enhances anti-tumor immunity. UIRN not only efficiently controls tumor progression alone but also exhibits adjuvant effects to chemotherapy and immunotherapy agents. The microbiota-regulating and tumor-suppressing functions of UIRN also work in the colitis-associated CRC model. With good biosafety, UIRN displays hopeful application prospects in CRC therapy. The anti-colorectal cancer (CRC) molecular targeting drug regorafenib-encapsulating nanoparticle is constructed with the amphiphilic inulin-ursodeoxycholic acid conjugate. Combining gut microbiota modulation by the inulin derivative and tumor microenvironment remodeling by regorafenib enhances anti-tumor immunity in CRC mouse models. The nanoparticle also serves as a good synergist of the chemo- or immunotherapy agent like oxaliplatin and the anti-programmed death-1 antibody. image