| Autor: |
Delavari B; Division of Nanobiotechnoloy, Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, 1417466191, Iran.; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran.; School of Pharmacy, Faculty of Medicine and health, University of Sydney, Sydney NSW 2016, Australia., Bigdeli B; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran.; School of Pharmacy, Faculty of Medicine and health, University of Sydney, Sydney NSW 2016, Australia., Mamashli F; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran., Gholami M; Department of Toxicology & Pharmacology, Faculty of Pharmacy, Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran 1416753955, Iran., Bazri B; Department of Chemistry, Amirkabir University of Technology, No. 424, Hafez Avenue, 1591634311 Tehran, Iran., Khoobi M; Biomaterials group, The Institute of Pharmaceutical Sciences Research Center (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran., Ghasemi A; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran., Baharifar H; Department of medical nanotechnology, Applied biophotonics research center, Science and Research branch, Islamic Azad University, Tehran, 1477893855, Iran., Dehghani S; Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Keshavarz blvd, 16 Azar St., Tehran 14145, Iran., Gholibegloo E; Department of Chemistry, Faculty of Science, University of Zanjan, 45371-38791 Zanjan, Iran., Amani A, Riahi-Alam N; Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Keshavarz blvd, 16 Azar St., Tehran 14145, Iran., Ahmadian S; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran., Goliaei B; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran., Asli NS, Rezayan AH; Division of Nanobiotechnoloy, Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, 1417466191, Iran., Saboury AA; Institute of Biochemistry and Biophysics, University of Tehran, Mailbox 13145-1384, Tehran, Iran., Varamini P; School of Pharmacy, Faculty of Medicine and health, University of Sydney, Sydney NSW 2016, Australia. |
| Abstrakt: |
A nanotheranostic system was developed using α-lactalbumin along with Fe 3 O 4 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 Fe 3 O 4 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 r 2 / r 1 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. |
