Cyclodextrin-derived Nano-medicine Suppresses the Progression of Colorectal Cancer

The malignancy of colorectal cancer is connected with inflammation, which poses great therapeutic challenges. To integratetherapeutic targets with anti-inflammation strategy, wedeveloped a biocompatible, non-covalent channel-type nanoparticles that was fabricated through host-guest complexation and multiple assemble of mannose-modified ?-cyclodextrin (M-?-CD) with Regorafenib (RG), denoted as RG@M-?-CD. For in vivo application, the channel-type formulation optimized the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer (CAC) and CT26 models, RG@M-?-CD was proven to be a targeted, safe and effective anti-tumor nanomedicine that suppressed tumor cells proliferation, lesioned neovascularization, and attanuated inflammation. To investigate the therapeutic mechanism of RG@M-?-CD nanomedicine, small pieces of colon tissue with tumors from control group and treatment group were used to perform the microarray for gene expression anaylsis. The RGnanomedicine is constructed through the host-guest assemble between mannose-modified ?-cyclodextrin (M-?-CD) and TKI Regorafenib (RG). With multiple assemble, the host-guest system is transformed into nanoparticle, denoted as RG@M-?-CD (or RG nanomedicine). Colitis-associated colon cancer model is established using AOM-DSS in C57 mice. The CAC mice are then treated with Rgnanomedicine or PBS. After treatment, the tumor loading colon tissues are selected to perform the mRNA expression evaluation.