Natural Polymers Decorated MOF-MXene Nanocarriers for Co-delivery of Doxorubicin/pCRISPR.

Abstract

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 μg.mL-1) and high (10 μg·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. 26% 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.