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.
Abstract. has been found to promote cell proliferation and survival. It has also been shown to exhibit an increased expression in a number of forms of cardiovascular disease. However, the mechanisms underlying the involvement of miR-21 in atherosclerosis remain to be elucidated. In the present study, it was demonstrated that miR-21 was upregulated in a time-dependent manner in response to high-concentration glucose stimulation in Raw 264.7 macrophages. High concentrations of glucose induce macrophage apoptosis. miR-21-inhibited macrophages treated with a normal concentration of glucose exhibited increased levels of cell apoptosis and augmented levels of activated caspase-3, while cells treated with an miR-21 inhibitor and a high concentration of glucose, revealed significantly increased levels of apoptosis. In addition, inhibition of miR-21 increased mRNA and protein levels of programmed cell death 4 (PDCD4), which, by contrast, were reduced in miR-21-inhibited cells that had been treated with a high concentration of glucose. In conclusion, miR-21 is sensitive to high-concentration glucose treatment in macrophages, and appears to have a protective effect in macrophage apoptosis induced by high concentrations of glucose via PDCD4.
Colorectal cancer (CRC) is the second most common cause of cancer incidence worldwide. Oral drug delivery systems (ODDS) have shown great promise for CRC therapy, but the delivery efficiency is still challenged by the dense intestinal mucus barrier and nonspecific interception of abnormally proliferated pathogenic bacteria. Herein, self-thermophoretic nanoparticles (CTPB) is presented to enhance intestinal mucus penetration and reduce pathogenic bacteria interception in CRC for efficient drug delivery. The nanoplatform introduces hollow mesoporous copper sulfide and is asymmetrically sprayed with titanium dioxide as the self-thermophoretic matrix. Based on the close relationship between pathogenic bacteria and CRC, the nanoplatform is camouflaged by the biomimetic membrane of Staphylococcus aureus to precisely anchor in the intestinal segment of CRC. After near-infrared laser irradiation, CTPB can effectively increase the intestinal mucus penetration efficiency by 2.7 folds, and decrease the pathogenic bacterial interception by 3.5 folds via the self-thermophoretic propulsion force. In orthotopic CRCbearing mice, CTPB vastly improved the drug delivery efficiency to CRC after oral administration, thus showing a 99.4% antitumor rate after three weeks of treatment, which provides new insight into oral drug delivery for CRC therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.