Bioactive nanomotor enabling efficient intestinal barrier penetration for colorectal cancer therapy

Oral drug delivery systems had natural potential for colorectal cancer drug therapy. While the drug delivery efficiency is severely hindered by the complex intestinal barriers, especially mucus and epithelium barriers, resulting in unsatisfactory therapeutic effects and limited clinical translation. In this work, a bioactive self-thermophoretic and gas dual-driven nanomotor is developed for colorectal cancer therapy through efficient intestinal mucus and epithelial barrier penetration. The nanomotor shows intestinal mucus barrier penetration and the paracellular pathway reversibly opening properties of intestinal epithelium barrier, increasing the delivery efficiency of cisplatin by 3.5 folds. Owing to the targeted delivery of cisplatin and the reduced side effects on normal intestinal tissues, the therapeutic efficiency of the nanomotor for colorectal cancer in vivo is as high as 98.6%. With autonomous and reversible intestinal barriers penetration property, the nanoplatform may innovate the current oral drug delivery. Oral drug delivery system has clinical potential for colorectal cancer (CRC) drug therapy but limited by the delivery efficiency when transporting through the formidable intestinal barriers. Here this group reports a Lactobacillus rhamnosus-engineered mesoporous silica nanosystem which effectively penetrates intestinal mucus and epithelial barrier, thereby delivering NO donor BNN6 and cisplatin for in vivo CRC tumor growth inhibition.