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Targeted Delivery of Doxorubicin by Sp5-52 Peptide Conjugated Exosome Nanoparticles Into Lung Tumor: An in Vitro and in Vivo Study Publisher



Moradi A1, 2 ; Shirangi A2 ; Asadi M3 ; Farokhi M4 ; Gholami M5 ; Aminianfar H6 ; Atyabi F7 ; Mottaghitalab F2 ; Dinarvand R2, 7
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
  4. 4. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
  5. 5. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  7. 7. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Drug Delivery Science and Technology Published:2024


Abstract

Here, SP5-52 peptide conjugated exosome nanostructures were developed for targeted delivery of Doxorubicin (DOX) into lung tumor. Exosomes extracted from the serum of Balb/c mice, were characterized in terms of structure and physicochemical properties. Based on the results, the size and zeta potential of exosome NPs were 67 nm and −5 mV, respectively, which was slightly increased after SP5-52 conjugation and DOX loading. The in vitro cell studies displayed that targeted DOX-loaded exosomes had higher cytotoxicity, cellular uptake, and accumulation in LL/2 cell lines compared with non-targeted DOX-loaded exosomes and control groups. Moreover, the therapeutic efficacy of the prepared formulations was evaluated in lung tumor bearing Balb/c mice within 21 days. Accordingly, targeted DOX-loaded exosomes had effectively treated the lung tumor in comparison to other groups. The rate of survival in the mice treated with targeted exosomes was also 35 % higher than other groups; while, the mortality rate was lower. The histopathological evaluation confirmed the accepted off-targeted properties of the targeted exosomes as lower toxicity was observed in different organs rather than lung. This study presents an effective anticancer drug delivery system for specific targeting of induced lung tumor, which could be useful in the treatment of malignant lung cancers in the future. © 2024 Elsevier B.V.
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