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Targeting reactive astrocytes by pH-responsive ligand-bonded polymeric nanoparticles in spinal cord injury

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Abstract

In spinal cord injuries, axonal regeneration decreases with the activation of astrocytes followed by glial scar formation. Targeting reactive astrocytes has been recently performed by unsafe viral vectors to inhibit gliosis. In the current study, biocompatible polymeric nanoparticles were selected as an alternative for viruses to target reactive astrocytes for further drug/gene delivery applications. Lipopolysaccharide-bonded chitosan-quantum dots/poly acrylic acid nanoparticles were prepared by ionic gelation method to target reactive astrocytes both in vitro and in spinal cord-injured rats. Owing to their biocompatibility and pH-responsive behavior, chitosan and poly acrylic acid were the main components of nanoparticles. Nanoparticles were then chemically labeled with quantum dots to track the cell uptake and electrostatically interacted with lipopolysaccharide as a targeting ligand. In vitro and in vivo studies were performed in triplicate and all data were expressed as the mean ± the standard error of the mean. Smart nanoparticles with optimum size (61.9 nm) and surface charge (+ 12.5 mV) successfully targeted primary reactive astrocytes extracted from the rat cerebral cortex. In vitro studies represented high cell viability (96%) in the exposure of biocompatible nanoparticles. The pH-responsive behavior of nanoparticles was proved by their internalization into the cell’s nuclei due to the swelling and endosomal escape of nanoparticles in acidic pH. In vivo studies demonstrated higher transfection of nanoparticles into reactive astrocytes compared to the neurons. pH-responsive ligand-bonded chitosan-based nanoparticles are good alternatives for viral vectors in targeted delivery applications for the treatment of spinal cord injuries.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Here, we acknowledge the Iran National Science Foundation (INSF) for supporting us in this research.

Funding

This work was supported by the Iran National Science Foundation (INSF) under Grant number [96004422]. Prof. Masoud Frounchi has received this research support from INSF.

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Authors and Affiliations

  1. Department of Chemical and Petroleum Engineering, Sharif University of Technology, Azadi Avenue, Tehran, Iran

    Parinaz Sabourian, Masoud Frounchi, Shohreh Mashayekhan & Seyed Sajad Ashraf

  2. Department of Brain and Cognitive Sciences, Cell Science Research Center, ROYAN Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Sahar Kiani, Masoumeh Zarei Kheirabadi & Yasaman Heydari

  3. Department of Stem Cell and Developmental Biology, Cell Science Research Center, ROYAN Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Sahar Kiani, Masoumeh Zarei Kheirabadi & Yasaman Heydari

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  1. Parinaz Sabourian
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  2. Masoud Frounchi
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  4. Shohreh Mashayekhan
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Contributions

Parinaz Sabourian: substantial contribution to the conception, design of the work, the acquisition, analysis, and interpretation of data; has drafted the work and substantively revised it. Masoud Frounchi: substantial contribution to the conception and design of the work and has substantively revised the work. Sahar Kiani: substantial contribution to the conception and design of the work and has substantively revised the work. Shohreh Mashayekhan: substantial contribution to the conception and has substantively revised the work. Masoumeh Zarei Kheirabadi: analysis, interpretation of data; and has drafted the work. Yasaman Heydari: analysis, interpretation of data; and has drafted the work. Seyed Sajad Ashraf: analysis, and interpretation of data.

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Correspondence to Masoud Frounchi.

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The animal studies were performed in line with the principles of the Declaration of the ROYAN Institute of Iran. Approval was granted by the ethics committee of the ROYAN Institute of Iran. No human studies have been performed in this research.

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Sabourian, P., Frounchi, M., Kiani, S. et al. Targeting reactive astrocytes by pH-responsive ligand-bonded polymeric nanoparticles in spinal cord injury. Drug Deliv. and Transl. Res. 13, 1842–1855 (2023). https://doi.org/10.1007/s13346-023-01300-3

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