Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Wang ZH

PROVIDER: S-EPMC9242589 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Wang Zhi-Hao ZH Chu Mengyu M Yin Na N Huang Wanting W Liu Wei W Zhang Zhenzhong Z Liu Junjie J Shi Jinjin J

Science advances 20220629 26

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. Further ...[more]

PMID: 35767627

Similar Datasets

Project description:Intestinal mucus is the first line of defense against intestinal pathogens. It acts as a physical barrier between epithelial tissues and the lumen that enteropathogens must overcome to establish a successful infection. We investigated the motile behavior of two Vibrio cholerae strains (El Tor C6706 and Classical O395) in mucus using single-cell tracking in unprocessed porcine intestinal mucus. We determined that V. cholerae can penetrate mucus using flagellar motility and that alkaline pH increases swimming speed and, consequently, improves mucus penetration. Microrheological measurements indicate that changes in pH between 6 and 8 (the physiological range for the human small intestine) had little effect on the viscoelastic properties of mucus. Finally, we determined that acidic pH promotes surface attachment by activating the mannose-sensitive hemagglutinin (MshA) pilus in V. cholerae El Tor C6706 without a measurable change in the total cellular concentration of the secondary messenger cyclic dimeric GMP (c-di-GMP). Overall, our results support the hypothesis that pH is an important factor affecting the motile behavior of V. cholerae and its ability to penetrate mucus. Therefore, changes in pH along the human small intestine may play a role in determining the preferred site for V. cholerae during infection.IMPORTANCE The diarrheal disease cholera is still a burden for populations in developing countries with poor sanitation. To develop effective vaccines and prevention strategies against Vibrio cholerae, we must understand the initial steps of infection leading to the colonization of the small intestine. To infect the host and deliver the cholera toxin, V. cholerae has to penetrate the mucus layer protecting the intestinal tissues. However, the interaction of V. cholerae with intestinal mucus has not been extensively investigated. In this report, we demonstrated using single-cell tracking that V. cholerae can penetrate intestinal mucus using flagellar motility. In addition, we observed that alkaline pH improves the ability of V. cholerae to penetrate mucus. This finding has important implications for understanding the dynamics of infection, because pH varies significantly along the small intestine, between individuals, and between species. Blocking mucus penetration by interfering with flagellar motility in V. cholerae, reinforcing the mucosa, controlling intestinal pH, or manipulating the intestinal microbiome will offer new strategies to fight cholera.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets