PMID- 34615960
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20240403
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Oct 6
TI  - Dual-ligated metal organic framework as novel multifunctional nanovehicle for 
      targeted drug delivery for hepatic cancer treatment.
PG  - 19808
LID - 10.1038/s41598-021-99407-5 [doi]
LID - 19808
AB  - 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 (NH(2)-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 NH(2)-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.
CI  - (c) 2021. The Author(s).
FAU - Fytory, Mostafa
AU  - Fytory M
AD  - Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and 
      Technology, Giza, 12578, Egypt.
AD  - Material Science and Nanotechnology Department, Faculty of Postgraduate Studies 
      for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, 62511, Egypt.
FAU - Arafa, Kholoud K
AU  - Arafa KK
AD  - Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and 
      Technology, Giza, 12578, Egypt.
FAU - El Rouby, Waleed M A
AU  - El Rouby WMA
AD  - Material Science and Nanotechnology Department, Faculty of Postgraduate Studies 
      for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, 62511, Egypt.
FAU - Farghali, Ahmed A
AU  - Farghali AA
AD  - Material Science and Nanotechnology Department, Faculty of Postgraduate Studies 
      for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, 62511, Egypt.
FAU - Abdel-Hafiez, Mahmoud
AU  - Abdel-Hafiez M
AD  - Department of Physics and Astronomy, Uppsala University, Box 516, 75120, Uppsala, 
      Sweden.
AD  - Department of Physics, Faculty of Science, Fayoum University, Fayoum, 63514, 
      Egypt.
FAU - El-Sherbiny, Ibrahim M
AU  - El-Sherbiny IM
AD  - Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and 
      Technology, Giza, 12578, Egypt. ielsherbiny@zewailcity.edu.eg.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211006
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Metal-Organic Frameworks)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage
MH  - Carcinoma, Hepatocellular/*drug therapy
MH  - Doxorubicin/*administration & dosage
MH  - Drug Carriers/*pharmacology
MH  - Fibroblasts
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/*drug therapy
MH  - Metal-Organic Frameworks/*pharmacology
PMC - PMC8494812
COIS- The authors declare no competing interests.
EDAT- 2021/10/08 06:00
MHDA- 2021/12/28 06:00
PMCR- 2021/10/06
CRDT- 2021/10/07 06:37
PHST- 2021/07/12 00:00 [received]
PHST- 2021/08/30 00:00 [accepted]
PHST- 2021/10/07 06:37 [entrez]
PHST- 2021/10/08 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2021/10/06 00:00 [pmc-release]
AID - 10.1038/s41598-021-99407-5 [pii]
AID - 99407 [pii]
AID - 10.1038/s41598-021-99407-5 [doi]
PST - epublish
SO  - Sci Rep. 2021 Oct 6;11(1):19808. doi: 10.1038/s41598-021-99407-5.