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Codelivery of Hif-1Α Sirna and Dinaciclib by Carboxylated Graphene Oxide-Trimethyl Chitosan-Hyaluronate Nanoparticles Significantly Suppresses Cancer Cell Progression Publisher Pubmed



Izadi S1, 2 ; Moslehi A1 ; Kheiry H3 ; Karoon Kiani F1 ; Ahmadi A4 ; Masjedi A5 ; Ghani S6 ; Rafiee B7 ; Karpisheh V1 ; Hajizadeh F1 ; Atyabi F8 ; Assali A8 ; Mirzazadeh Tekie FS9 ; Namdar A10 Show All Authors
Authors
  1. Izadi S1, 2
  2. Moslehi A1
  3. Kheiry H3
  4. Karoon Kiani F1
  5. Ahmadi A4
  6. Masjedi A5
  7. Ghani S6
  8. Rafiee B7
  9. Karpisheh V1
  10. Hajizadeh F1
  11. Atyabi F8
  12. Assali A8
  13. Mirzazadeh Tekie FS9
  14. Namdar A10
  15. Ghalamfarsa G11
  16. Sojoodi M12
  17. Jadidiniaragh F1, 13
Show Affiliations
Authors Affiliations
  1. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran
  4. 4. Department of Chemical and Materials Engineering, The University of Alabama in Huntsville, Huntsville, 35899, AL, United States
  5. 5. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Department of Biology, Faculty of Basic Science, Payame Noor University, Tehran, Iran
  8. 8. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Oncology, Cross Cancer Institute, The University of Alberta, Edmonton, AB, Canada
  11. 11. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  12. 12. Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, United States
  13. 13. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Pharmaceutical Research Published:2020


Abstract

Purpose: Hypoxia-inducible factor (HIF) is one of the critical components of the tumor microenvironment that is involved in tumor development. HIF-1α functionally and physically interacts with CDK1, 2, and 5 and stimulates the cell cycle progression and Cyclin-Dependent Kinase (CDK) expression. Therefore, hypoxic tumor microenvironment and CDK overexpression lead to increased cell cycle progression and tumor expansion. Therefore, we decided to suppress cancer cell expansion by blocking HIF-1α and CDK molecules. Methods: In the present study, we used the carboxylated graphene oxide (CGO) conjugated with trimethyl chitosan (TMC) and hyaluronate (HA) nanoparticles (NPs) loaded with HIF-1α-siRNA and Dinaciclib, the CDK inhibitor, for silencing HIF-1α and blockade of CDKs in CD44-expressing cancer cells and evaluated the impact of combination therapy on proliferation, metastasis, apoptosis, and tumor growth. Results: The results indicated that the manufactured NPs had conceivable physicochemical properties, high cellular uptake, and low toxicity. Moreover, combination therapy of cancer cells using CGO-TMC-HA NPs loaded with HIF-1α siRNA and Dinaciclib (SCH 727965) significantly suppressed the CDKs/HIF-1α and consequently, decreased the proliferation, migration, angiogenesis, and colony formation in tumor cells. Conclusions: These results indicate the ability of CGO-TMC-HA NPs for dual drug/gene delivery in cancer treatment. Furthermore, the simultaneous inhibition of CDKs/HIF-1α can be considered as a novel anti-cancer treatment strategy; however, further research is needed to confirm this treatment in vivo. [Figure not available: see fulltext.] © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
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