Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment

Abstract In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery sy...

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Main Authors: Mostafa Fytory, Kholoud K. Arafa, Waleed M. A. El Rouby, Ahmed A. Farghali, Mahmoud Abdel-Hafiez, Ibrahim M. El-Sherbiny
Format: Article
Language:English
Published: Nature Portfolio 2021-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-99407-5
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author Mostafa Fytory
Kholoud K. Arafa
Waleed M. A. El Rouby
Ahmed A. Farghali
Mahmoud Abdel-Hafiez
Ibrahim M. El-Sherbiny
author_facet Mostafa Fytory
Kholoud K. Arafa
Waleed M. A. El Rouby
Ahmed A. Farghali
Mahmoud Abdel-Hafiez
Ibrahim M. El-Sherbiny
author_sort Mostafa Fytory
collection DOAJ
description Abstract In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.
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spelling doaj.art-c0dd6fd376464b3e89fe47611bae91022022-12-21T19:10:45ZengNature PortfolioScientific Reports2045-23222021-10-0111111310.1038/s41598-021-99407-5Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatmentMostafa Fytory0Kholoud K. Arafa1Waleed M. A. El Rouby2Ahmed A. Farghali3Mahmoud Abdel-Hafiez4Ibrahim M. El-Sherbiny5Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and TechnologyNanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and TechnologyMaterial Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef UniversityMaterial Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef UniversityDepartment of Physics and Astronomy, Uppsala UniversityNanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and TechnologyAbstract In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.https://doi.org/10.1038/s41598-021-99407-5
spellingShingle Mostafa Fytory
Kholoud K. Arafa
Waleed M. A. El Rouby
Ahmed A. Farghali
Mahmoud Abdel-Hafiez
Ibrahim M. El-Sherbiny
Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
Scientific Reports
title Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
title_full Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
title_fullStr Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
title_full_unstemmed Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
title_short Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
title_sort dual ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment
url https://doi.org/10.1038/s41598-021-99407-5
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