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Engineered Hyaluronic Acid-Decorated Niosomal Nanoparticles for Controlled and Targeted Delivery of Epirubicin to Treat Breast Cancer Publisher



Mansoorikermani A1 ; Khalighi S1 ; Akbarzadeh I1 ; Niavol FR2 ; Motasadizadeh H3, 7 ; Mahdieh A3 ; Jahed V4 ; Abdinezhad M5 ; Rahbariasr N6 ; Hosseini M1 ; Ahmadkhani N1 ; Panahi B1 ; Fatahi Y3, 7 ; Mozafari M8 Show All Authors
Authors
  1. Mansoorikermani A1
  2. Khalighi S1
  3. Akbarzadeh I1
  4. Niavol FR2
  5. Motasadizadeh H3, 7
  6. Mahdieh A3
  7. Jahed V4
  8. Abdinezhad M5
  9. Rahbariasr N6
  10. Hosseini M1
  11. Ahmadkhani N1
  12. Panahi B1
  13. Fatahi Y3, 7
  14. Mozafari M8
  15. Kumar AP9, 10
  16. Mostafavi E11, 12
Show Affiliations
Authors Affiliations
  1. 1. Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran
  2. 2. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  3. 3. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Rudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Institute of General Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka St. 3/3, LV, Riga, 1007, Latvia
  5. 5. School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
  6. 6. Polymer Research Laboratory, Department of Chemistry, Sharif University of Technology, Tehran, Iran
  7. 7. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
  10. 10. NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
  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: Materials Today Bio Published:2022


Abstract

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer. © 2022 The Authors
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