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Ph-Responsive Chitosan-Adorned Niosome Nanocarriers for Co-Delivery of Drugs for Breast Cancer Therapy Publisher



Karimifard S1 ; Rezaei N2 ; Jamshidifar E3 ; Moradi Falah Langeroodi S4 ; Abdihaji M5 ; Mansouri A6 ; Hosseini M7 ; Ahmadkhani N8 ; Rahmati Z9 ; Heydari M10 ; Vosough M2 ; Akbarzadeh I2, 7 ; Mostafavi E11, 12
Authors
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Authors Affiliations
  1. 1. Stem Cells Research Center, Tissue Engineering and Regenerative Medicine Institute, Islamic Azad University, Central Tehran Branch, Tehran, 1955847781, Iran
  2. 2. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 16635148, Iran
  3. 3. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
  4. 4. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 7616913555, Iran
  5. 5. Department of Biology, The Center for Genomics and Bioinformatics, Indiana University, Bloomington, 47405-7000, IN, United States
  6. 6. School of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, 19395-1495, Iran
  7. 7. Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, 1458889694, Iran
  8. 8. School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, 97331, OR, United States
  9. 9. Department of Chemical Engineering, University of South Carolina, Columbia, 29208, SC, United States
  10. 10. Department of Cell and Molecular Biology, Faculty of Biological Science, University of Kharazmi, Tehran, 199389373, Iran
  11. 11. Stanford Cardiovascular Institute, Stanford University, School of Medicine, Stanford, 94305, CA, United States
  12. 12. Department of Medicine, Stanford University, School of Medicine, Stanford, 94305, CA, United States

Source: ACS Applied Nano Materials Published:2022


Abstract

Breast cancer incidence has increased in recent decades. In the present study, an optimum formulation of chitosan (CS)-adorned niosome-based nanocarriers for co-delivery of doxorubicin (DOX) and vincristine (VIN) was developed for the treatment of breast cancer to reduce drug doses and overcome multidrug resistance. The three-level Box-Behnken method was utilized to optimize the particles in terms of size, polydispersity index (PDI), entrapment efficacy (EE (%)), and percent of drug release (%). The release rate of two drugs from CS-adorned nanoparticles (DOX+VIN/Nio/CS) in acidic and physiological pH is less than uncoated niosome (DOX+VIN/Nio). In addition, acidic pH increases the release rate of drugs from these formulations. The size, polydispersity index, and entrapment efficacy of nanoparticles were more stable at 4 °C compared to 25 °C. MTT assay showed that the IC50of DOX+VIN/Nio/CS is the lowest value between all fabricated formulations. We evaluated the cancer metastasis and migration (MMP2, MMP9) and transcriptional targets for the tumor suppressor protein (Bax, Bcl2) that induces cell cycle arrest or apoptosis in response to DNA. Bax gene was highly expressed, while the Bcl2, MMP2, and MMP9 genes decreased in DOX+VIN/Nio/CS compared to control, free forms of DOX, VIN, DOX+VIN, and DOX+VIN/Nio. DOX+VIN/Nio/CS inhibited cell migration and increased apoptosis, cell uptake, and endocytosis in human SKBR3 breast cancer cells compared to DOX, VIN, DOX+VIN. These in vitro data are promising to treat breast cancer with advanced pH-responsive drug release nanoformulations. © 2022 American Chemical Society. All rights reserved.
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