Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified gamma -cyclodextrin (M-gamma -CD) with Regorafenib (RG), RG@M-gamma -CD CNPs. In addition to its carrier role, M-gamma -CD serves as a targeting device and participates in TME regulation. RG@M-gamma -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-gamma -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-gamma -CD CNPs as a potential strategy for CRC treatment. Regorafenib is a multi-kinase inhibitor in use for the treatment of colorectal cancer (CRC). To improve drug pharmacokinetics and bioavailability, here the authors design mannose-modified cyclodextrin-based host-guest complexes loaded with Regorafenib, showing anti-tumor responses in preclinical models of CRC.

Automated summary

A novel type of nanoparticles, CNPs, was developed for the treatment of colorectal cancer by targeting macrophages and modulating the tumor microenvironment, significantly improving the efficacy of the drug.