Journal
ACS APPLIED BIO MATERIALS
Volume 4, Issue 6, Pages 5106-5121Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.1c00332
Keywords
co-delivery; pCRISPR; MOF-5; MXene; biomaterials; chitosan; alginate
Funding
- Sharif University of Technology Research Council
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A one-pot and facile method with assistance of high gravity was used to synthesize inorganic nanostructures for efficient co-delivery of drug and gene. The bioavailability and interaction with pCRISPR was enhanced by coating the nanomaterial with alginate and chitosan, leading to excellent cell viability and comprehensive cytotoxicity studies. The polymer-coated nanosystems showed superior relative cell viability, with chitosan-coated nanocarriers demonstrating over 60% relative cell viability on average across all cell lines.
A one-pot and facile method with assistance of high gravity was applied for the synthesis of inorganic two-dimensional MOF-5 embedded MXene nanostructures. The innovative inorganic MXene/MOF-5 nanostructure was applied in co-delivery of drug and gene, and to increase its bioavailability and interaction with the pCRISPR, the nanomaterial was coated with alginate and chitosan. The polymer-coated nanosystems were fully characterized, and the sustained DOX delivery and comprehensive cytotoxicity studies were conducted on the HEK-293, PC12, HepG2, and HeLa cell lines, demonstrating acceptable and excellent cell viability at both very low (0.1 mu g.mL(-1)) and high (10 mu g.mL(-1)) concentrations. The chitosan-coated nanocarriers showed superior relative cell viability compared to others, more than 60% on average of relative cell viability in all of the cell lines. Then, alginate-coated nanocarriers ranked at second place on the higher relative cell viability, more than 50% on average for all of the cell lines. Also, MTT results showed a complete dose-dependence, and by increasing the time of treatment from 24 to 72 h, the relative cell viability decreased by a meaningful slope; however, this decrease was optimized by coating the nanocarrier with chitosan and alginate. The nanosystems were also tagged with pCRISPR to analyze the potential application in the co-delivery of drug/gene. CLSM images of the HEK-293 and HeLa cell lines unveiled successful delivery of pCRISPR into the cells, and the enhanced green fluorescent protein (EGFP) reached up to ca. 2.6% for the HeLa cell line. Also, a considerable drug payload of 35.7% was achieved, which would be because of the interactions between the nanocarrier and the doxorubicin. In this unprecedented report pertaining to the synthesis of MXene assisted by a MOF and high-gravity technique, the methodology and the optimized ensuing MXene/MOF-5 nanosystems can be further developed for the co-delivery of drug/gene in animal models.
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