The malignancy of colorectal cancer is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for colorectal cancer are limited. To integrate therapeutic targeting with tumor microenvironment reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in tumor microenvironment regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG’s anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.
Bai, H., Wang, J., Phan, C.U. et al. (2021) Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment. Nat Commun 12, 759. https://doi.org/10.1038/s41467-021-21071-0