Tumor necrosis factor-alpha antibody labeled-polyethylene glycol-coated nanoparticles: A mesenchymal stem cells-based drug delivery system in the rat model of cisplatin-induced nephrotoxicity

Vet World Vol.15 October-2022 Article-14

Research Article

Veterinary World, 15(10): 2475-2490

https://doi.org/10.14202/vetworld.2022.2475-2490

Faten A. M. Abo-Aziza¹, Saleh M. Albarrak², Abdel-Kader A. Zaki^2,3, and Shaymaa E. El-Shafey⁴

1. Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, Cairo, Egypt.
2. Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia.
3. Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
4. Department of Physical Chemistry, National Research Centre, Cairo, Egypt.

Background and Aim: A delivery system consisting of bone marrow mesenchymal stem cells (MSCs) loaded with polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (SPIONs) was constructed to treat a rat model of cisplatin (Cis)-induced nephrotoxicity with 1/10 of the common dose of anti-tumor necrosis factor-alpha (TNF-α) antibodies (infliximab).

Materials and Methods: Morphology, size, crystallinity, molecular structure, and magnetic properties of uncoated and PEG-coated SPIONs were analyzed. A delivery system consisting of MSCs containing infliximab-labeled PEG-coated SPIONs (Infliximab-PEG-SPIONs-MSCs) was generated and optimized before treatment. Fifty female Wistar rats were divided into five equal groups: Group 1: Untreated control; Group 2 (Cis): Rats were administered Cis through intraperitoneal (i.p.) injection (8 mg/kg) once a week for 4 weeks; Group 3 (Infliximab): Rats were injected once with infliximab (5 mg/kg), i.p. 3 days before Cis administration; Group 4 (Cis + MSCs): Rats were injected with Cis followed by an injection of 2 × 106 MSCs into the tail vein twice at a 1-week interval; and Group 5 (Cis + Infliximab (500 μg/kg)-PEG-SPIONs-MSCs): Rats were injected with the delivery system into the tail vein twice at a 1-week interval. Besides histological examination of the kidney, the Doppler ultrasound scanner was used to scan the kidney with the Gray-color-spectral mode.

Results: In vivo, intra-renal iron uptake indicates the traffic of the delivery system from venous blood to renal tissues. Cis-induced nephrotoxicity resulted in a significant increase in TNF-α and malondialdehyde (MDA) (p < 0.05), bilirubin, creatinine, and uric acid (p < 0.01) levels compared with the untreated control group. The different treatments used in this study resulted in the amelioration of some renal parameters. However, TNF-α levels significantly decreased in Cis + Infliximab and Cis + MSCs (p < 0.05) groups. The serum levels of MDA significantly decreased in Cis + Infliximab (p < 0.05), Cis + MSCs (p < 0.05), and Cis + Infliximab-PEG-SPIONs-MSCs (p < 0.01). Furthermore, the serum activities of antioxidant enzymes were significantly elevated in the Cis + MSCs and Cis + Infliximab-PEG-SPIONs-MSCs groups (p < 0.05) compared to the Cis-induced nephrotoxicity rat model.

Conclusion: With the support of the constructed MSCs-SPIONs infliximab delivery system, it will be possible to track and monitor cell homing after therapeutic application. This infliximab-loading system may help overcome some challenges regarding drug delivery to the target organ, optimize therapeutics' efficacy, and reduce the dose. The outcomes of the current study provide a better understanding of the potential of combining MSCs and antibodies-linked nanoparticles for the treatment of nephrotoxicity. However, further investigation is recommended using different types of other drugs. For new approaches development, we should evaluate whether existing toxicity analysis and risk evaluation strategies are reliable and enough for the variety and complexity of nanoparticles. Keywords: cisplatin, drug delivery system, infliximab, mesenchymal stem cells, nephrotoxicity, superparamagnetic iron oxide nanoparticles, tumor necrosis factor-alpha.

Keywords: cisplatin, drug delivery system, infliximab, mesenchymal stem cells, nephrotoxicity, superparamagnetic iron oxide nanoparticles, tumor necrosis factor-alpha.

How to cite this article: Abo-Aziza FAM, Albarrak SM, Zaki AA, and El-Shafey SE (2022) Tumor necrosis factor-alpha antibody labeled-polyethylene glycol-coated nanoparticles: A mesenchymal stem cells-based drug delivery system in the rat model of cisplatin-induced nephrotoxicity, Veterinary World, 15(10): 2475–2490.

Received: 14-06-2022 Accepted: 12-09-2022 Published online: 29-10-2022

Corresponding author: Faten A. M. Abo-Aziza E-mail: faten.aboaziza@gmail.com

DOI: 10.14202/vetworld.2022.2475-2490

Copyright: Abo-Aziza FAM, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.