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Theranostic Α-Lactalbumin-Polymer-Based Nanocomposite As a Drug Delivery Carrier for Cancer Therapy Publisher Pubmed



Delavari B1, 2, 3 ; Bigdeli B2, 3 ; Mamashli F2 ; Gholami M4 ; Bazri B5 ; Khoobi M6, 7 ; Ghasemi A2 ; Baharifar H9 ; Dehghani S10 ; Gholibegloo E11 ; Amani A8 ; Riahialam N10 ; Ahmadian S2 ; Goliaei B2 Show All Authors
Authors
  1. Delavari B1, 2, 3
  2. Bigdeli B2, 3
  3. Mamashli F2
  4. Gholami M4
  5. Bazri B5
  6. Khoobi M6, 7
  7. Ghasemi A2
  8. Baharifar H9
  9. Dehghani S10
  10. Gholibegloo E11
  11. Amani A8
  12. Riahialam N10
  13. Ahmadian S2
  14. Goliaei B2
  15. Asli NS12, 13
  16. Rezayan AH1
  17. Saboury AA2
  18. Varamini P3
Show Affiliations
Authors Affiliations
  1. 1. Division of Nanobiotechnoloy, Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, 1417466191, Iran
  2. 2. Institute of Biochemistry and Biophysics, University of Tehran, Mailbox, Tehran, 13145-1384, Iran
  3. 3. School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, 2016, NSW, Australia
  4. 4. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
  5. 5. Department of Chemistry, Amirkabir University of Technology, No. 424, Hafez Avenue, Tehran, 1591634311, Iran
  6. 6. Biomaterials Group, Institute of Pharmaceutical Sciences Research Center (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
  7. 7. Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center (MBRC), Faculty of Pharmacy, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
  8. 8. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1416753955, Iran
  9. 9. Department of Medical Nanotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, 1477893855, Iran
  10. 10. Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Keshavarz blvd, 16 Azar St., Tehran, 14145, Iran
  11. 11. Department of Chemistry, Faculty of Science, University of Zanjan, Zanjan, 45371-38791, Iran
  12. 12. Sydney Medical School, Faculty of Medicine and Health, School of Dentistry, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, 2145, NSW, Australia
  13. 13. Discipline of Oral Biosciences, School of Dentistry, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, 2145, NSW, Australia

Source: ACS Biomaterials Science and Engineering Published:2019


Abstract

A nanotheranostic system was developed using α-lactalbumin along with Fe3O4 nanoparticles as an magnetic resonance imaging (MRI) contrast agent for medical imaging and doxorubicin as the therapeutic agent. α-lactalbumin was precipitated and cross-linked using poly(ethylene glycol) and glutaraldehyde. Besides, polyethylenimine was applied to increase the number of amine groups during cross-linking between α-lactalbumin and Fe3O4 nanoparticles. Interestingly, 90% of the initial protein used for the coaggregation process was incorporated in the prepared 130 nm nanocomposites, which facilitated the 85% doxorubicin loading. Formation of pH-sensitive imine bonds between glutaraldehyde and amine groups on α-lactalbumin and polyethylenimine resulted in higher release of doxorubicin at acidic pHs and consequently development of a pH-sensitive nanocarrier. The designed nanocomposite was less immunogenic owing to stimulating the production of less amounts of C3a, C5a, platelet factor 4, glycoprotein IIb/IIIa, platelet-derived β-thromboglobulin, interleukin-6, and interleukin-1β compared to the free doxorubicin. Furthermore, 1000 μg/mL nanocomposite led to 0.2% hemolytic activity, much less than the 5% standard limit. The void nanocarrier induced no significant level of cytotoxicity in breast cancer and normal cells following 96 h incubation. The doxorubicin-loaded nanocomposite presented higher cytotoxicity, apoptosis induction, and doxorubicin uptake in cancer cells than free doxorubicin. Conversely, lower cytotoxicity, apoptosis induction, and doxorubicin uptake were observed in normal cells treated with the doxorubicin-loaded nanocarrier compared to free doxorubicin. In line with the results of in vitro experiments, in vivo studies on tumor-bearing mice showed more suppression of tumor growth by the doxorubicin-loaded nanocomposite compared to the free drug. Moreover, the pharmacokinetic study revealed slow release of doxorubicin from the nanocomposite. Besides, in vitro and in vivo MRI studies presented a higher r2/r1 ratio and comparable contrast to the commercially available DOTAREM, respectively. Our findings suggest that this new nanocomposite is a promising nanotheranostic system with promising potential for cancer therapy and diagnosis. © 2019 American Chemical Society.
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