Distant
metastases and
chemotherapy repellency are the key causes of
colorectal cancer (CRC)-related mortality.
Regorafenib, an oral multi-
kinase inhibitor approved for treating advanced CRC with distant
metastases and/or chemo-resistance, however only improves median overall survival by 1.4 months. Such limited
therapeutic effect is likely due to the low bioavailability of orally administered hydrophobic
regorafenib. A
regorafenib nanodrug is fabricated by one-step self-assembly with a clinically often-used fluorescent agent (
indocyanine green) for overcoming
regorafenib's limitations, towards improving
regorafenib's therapeutic efficacy in advanced CRC. This nanodrug (nanoRF) was characterized, and its antitumor effects were assessed in three preclinical CRC models. NanoRF converts
regorafenib's delivery approach from oral to intravenous with a significantly high encapsulation efficacy of
regorafenib (96%) and a long-time colloidal stability. Nanodrug (nanoRF) markedly prolongs
regorafenib's blood circulation by halving clearance rate, and enhances
regorafenib's
tumor accumulation. Across three preclinical CRC models (xenografted
tumor, chemodrug-resistant xenografted
tumor, and liver
metastasis), nanoRF drastically enhances
regorafenib's
tumor inhibiting efficacy by 0.5-4 folds and effectively extends survival by 0.5-5 folds. This
regorafenib nanodrug is a simple, safe, and efficient therapeutic nanodrug for treating advanced CRC with a ready-to-be-clinically-translated potential.