Polymer-Coated NH2-UiO-66 for the Codelivery of DOX/pCRISPR

ACS Appl Mater Interfaces. 2021 Mar 10;13(9):10796-10811. doi: 10.1021/acsami.1c01460. Epub 2021 Feb 23.

Abstract

Herein, the NH2-UiO-66 metal organic framework (MOF) has been green synthesized with the assistance of high gravity to provide a suitable and safe platform for drug loading. The NH2-UiO-66 MOF was characterized using a field-emission scanning electron microscope, transmission electron microscope (TEM), X-ray diffraction, and zeta potential analysis. Doxorubicin was then encapsulated physically on the porosity of the green MOF. Two different stimulus polymers, p(HEMA) and p(NIPAM), were used as the coating agents of the MOFs. Doxorubicin was loaded onto the polymer-coated MOFs as well, and a drug payload of more than 51% was obtained, which is a record by itself. In the next step, pCRISPR was successfully tagged on the surface of the modified MOFs, and the performance of the final nanosystems were evaluated by the GFP expression. In addition, successful loadings and internalizations of doxorubicin were investigated via confocal laser scanning microscopy. Cellular images from the HeLa cell line for the UiO-66@DOX@pCRISPR and GMA-UiO-66@DOX@pCRISPR do not show any promising and successful gene transfections, with a maximum EGFP of 1.6%; however, the results for the p(HEMA)-GMA-UiO-66@DOX@pCRISPR show up to 4.3% transfection efficiency. Also, the results for the p(NIPAM)-GMA-UiO-66@DOX@pCRISPR showed up to 6.4% transfection efficiency, which is the first and superior report of a MOF-based nanocarrier for the delivery of pCRISPR. Furthermore, the MTT assay does not shown any critical cytotoxicity, which is a promising result for further biomedical applications. At the end of the study, the morphologies of all of the nanomaterials were screened after drug and gene delivery procedures and showed partial degradation of the nanomaterial. However, the cubic structure of the MOFs has been shown in TEM, and this is further proof of the stability of these green MOFs for biomedical applications.

Keywords: CRISPR; MOF; drug delivery; gene delivery; green chemistry.

MeSH terms

  • Acrylic Resins / chemistry*
  • Acrylic Resins / toxicity
  • Adsorption
  • CRISPR-Cas Systems*
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism*
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Drug Liberation
  • Gene Transfer Techniques
  • Green Chemistry Technology
  • Green Fluorescent Proteins / genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Metal-Organic Frameworks / chemistry*
  • Metal-Organic Frameworks / toxicity
  • Polyhydroxyethyl Methacrylate / chemistry*
  • Polyhydroxyethyl Methacrylate / toxicity
  • Porosity

Substances

  • Acrylic Resins
  • Drug Carriers
  • Metal-Organic Frameworks
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • poly-N-isopropylacrylamide
  • Polyhydroxyethyl Methacrylate
  • Doxorubicin