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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

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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