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Inhibition of Cd73 Using Folate Targeted Nanoparticles Carrying Anti-Cd73 Sirna Potentiates Anticancer Efficacy of Dinaciclib Publisher Pubmed



Hallaj S1, 2 ; Heydarzadeh Asl S1 ; Alian F3 ; Farshid S3 ; Eshaghi FS4 ; Namdar A5 ; Atyabi F6 ; Masjedi A7 ; Hallaj T8 ; Ghorbani A2 ; Ghalamfarsa G9 ; Sojoodi M10 ; Jadidiniaragh F1, 11
Authors
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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. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  4. 4. Department of Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  5. 5. Department of Oncology, Cross Cancer Institute, The University of Alberta, Edmonton, AB, Canada
  6. 6. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  8. 8. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, 5714783734, Iran
  9. 9. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  10. 10. Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, United States
  11. 11. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Life Sciences Published:2020


Abstract

Conventional therapeutic methods against cancer, including chemotherapy, radiotherapy, surgery, and combination therapy, have exhibited different toxicity levels due to their unspecific mechanism of action. To overcome the challenges facing conventional cancer therapies, newly developed methods are being investigated. Significant levels of specificity, remarkable accumulation at the tumor site, limited side effects, and minimal off-target effects enable the newly synthesized nanoparticles (NPs) to become the preferred drug delivery method in anticancer therapeutic approaches. According to the literature, CD73 has a pivotal role in cancer progression and resistance to chemotherapy and radiotherapy. Therefore, CD73 has attracted considerable attention among scientists to target this molecule. Accordingly, FDA approved CDK inhibitors such as Dinaciclib that blocks CDK1, 2, 5, and 9, and exhibits significant anticancer activity. So in this study, we intended to simultaneously suppress CD73 and CDKs in cancer cells by using the folic acid (FA)-conjugated chitosan-lactate (CL) NPs loaded with anti-CD73 siRNA and Dinaciclib to control tumor progression and metastasis. The results showed that NPs could effectively transfect cancer cells in a FA receptor-dependent manner leading to suppression of proliferation, survival, migration, and metastatic potential. Moreover, the treatment of tumor-bearing mice with this combination strategy robustly inhibited tumor growth and enhanced survival time in mice. These findings imply the high potential of FA-CL NPs loaded with anti-CD73 siRNA and Dinaciclib for use in cancer treatment shortly. © 2020
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