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Doxorubicin-Loaded Niosomes Functionalized With Gelatine and Alginate As Ph-Responsive Drug Delivery System: A 3D Printing Approach Publisher Pubmed



Zaer M1 ; Moeinzadeh A2 ; Abolhassani H3 ; Rostami N4 ; Tavakkoli Yaraki M5 ; Seyedi SA6 ; Nabipoorashrafi SA6 ; Bashiri Z7 ; Moeinabadibidgoli K8 ; Moradbeygi F9 ; Farmani AR10 ; Hosseinkhannazer N11
Authors
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Authors Affiliations
  1. 1. Biomedical Engineering Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran
  2. 2. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Biomedical Engineering, University of Rochester, Rochester, 14627, NY, United States
  4. 4. Department of Chemistry, Amirkabir University of Technology, Tehran, Iran
  5. 5. School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, 2109, NSW, Australia
  6. 6. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran, Iran
  7. 7. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  9. 9. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
  10. 10. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
  11. 11. Gastroenterology and Liver Diseases Research Center, Research, Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: International Journal of Biological Macromolecules Published:2023


Abstract

Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining 3D printing and nanocarriers has created new opportunities in cancer treatment. In this work, 3D-printed gelatin-alginate nanocomposites containing doxorubicin-loaded niosomes (Nio-DOX@GT-AL) were recruited as an advanced potential pH-sensitive drug delivery system. Morphology, degradation, drug release, flow cytometry, cell cytotoxicity, cell migration, caspase activity, and gene expression of nanocomposites and controls (Nio-DOX and Free-DOX) were evaluated. Results show that the obtained niosome has a spherical shape and size of 60–80 nm. Sustained drug release and biodegradability were presented by Nio-DOX@GT-AL and Nio-DOX. Cytotoxicity analysis revealed that the engineered Nio-DOX@GT-AL scaffold had 90 % cytotoxicity against breast cancer cells (MCF-7), whereas exhibited <5 % cytotoxicity against the non-tumor breast cell line (MCF-10A), which was significantly more than the antitumor effect of the control samples. Scratch-assay as an indicator cell migration demonstrated a reduction of almost 60 % of the covered surface. Gene expression could provide an explanation for the antitumor effect of engineered nanocarriers, which significantly reduced metastasis-promoting genes (Bcl2, MMP-2, and MMP-9), and significantly enhanced the expression and activity of genes that promote apoptosis (CASP-3, CASP-8, and CASP-9). Also, considerable inhibition of metastasis-associated genes (Bax and p53) was observed. Moreover, flow-cytometry data demonstrated that Nio-DOX@GT-AL decreased necrosis and enhanced apoptosis drastically. The findings of this research can confirm that employing 3D-printing and niosomal formulation can be an effective strategy in designing novel nanocarriers for efficient drug delivery applications. © 2023 The Authors
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