Biological chemotaxis-guided self-thermophoretic nanoplatform augments colorectal cancer therapy through autonomous mucus penetration

Oral drug delivery systems have great potential to treat colorectal cancer (CRC). However, the drug delivery efficiency is restricted by limited CRC-related intestine positioning and dense mucus barrier. Here, we present a biological chemotaxis-guided self-thermophoretic nanoplatform that facilitates precise intestinal positioning and autonomous mucus penetration. The nanoplatform introduces asymmetric platinum-sprayed mesoporous silica to achieve autonomous movement in intestinal mucus. Furthermore, inspired by the intense interaction between pathogenic microbes and CRC, the nanoplatform is camouflaged by Staphylococcus aureus membrane to precisely anchor in CRC-related intestine. Owing to 4.3-fold higher biological chemotactic anchoring of CRC-related intestine and 14.6-fold higher autonomous mucus penetration performance, the nanoplatform vastly improves the oral bioavailability of cisplatin, leading to a tumor inhibition rate of 99.1% on orthotopic CRC-bearing mice. Together, the exquisitely designed nanoplatform to overcome multiple physiological barriers provides a new horizon for the development of oral drug delivery systems.

Automated summary

This study presents a biological chemotaxis-guided self-thermophoretic nanoplatform that improves the efficacy of oral drug delivery systems for colorectal cancer treatment. The nanoplatform achieves precise intestinal positioning and autonomous mucus penetration by introducing platinum-sprayed mesoporous silica and camouflaging with Staphylococcus aureus membrane. The nanoplatform significantly enhances the oral bioavailability of cisplatin and exhibits a high tumor inhibition rate in CRC-bearing mice.