Engineered platelet extracellular vesicles delivering miR-320a promote proliferation, neuronal differentiation, and dopaminergic function in SH-SY5Y cells by targeting ITGβ1

Platelet-derived extracellular vesicles (PEVs) hold promise as drug delivery vehicles, due to their abundance, clinical accessibility, and ability to cross the blood-brain barrier. Building on our previous identification of miR-320a as a candidate for schizophrenia, we engineered PEVs to deliver miR-320a via electroporation. The resulting PEVs-miR-320a were readily internalized by SH-SY5Y cells.

PEVs-miR-320a—but not free miR-320a, native PEVs, or vehicle—markedly potentiated SH-SY5Y cell viability and enhanced retinoic acid (RA)-induced neuronal differentiation. In RA-differentiated SH-SY5Y cells, PEVs-miR-320a selectively elevated extracellular dopamine levels without affecting glutamate or serotonin. Mechanistically, PEV-mediated delivery elevated intracellular miR-320a, which in turn downregulated its target, integrin β1 (ITGβ1).

Together with our previously published in vivo evidence showing that PEVs-miR-320a improved behavioral abnormalities in an MK-801-induced schizophrenia-like rat model, the present study provides cellular-level proof-of-concept evidence that PEVs can deliver miR-320a and modulate neuronal phenotype-related readouts, supporting further investigation of the miR-320a/ITGβ1 pathway as a candidate therapeutic/regulatory axis for schizophrenia. Ultra-performance liquid chromatography-tandem mass spectrometry All the pictures were created in https://BioRender.com and GraphPad Prism. This work was supported by: (1) Science and Technology Program of Sichuan Province (Grant No. 2023YF50504); (2) Health Commission of Sichuan Province Medical Science and Technology Program (Grant No. 25QNMP032); (3) Luzhou Medical Association Science and Technology Program Project (Grant No. 2025-YXX-KY-M-073).

Department of Transfusion, Zigong First People’s Hospital, Zigong, 643000, China Department of Clinical Laboratory, Luzhou Longmatan District People’s Hospital, Guanyinbao Road 2#, Longmatan District, Luzhou, 646000, Sichuan Province, China Department of Transfusion, Guanghan People’s Hospital, Deyang, 618300, China Department of Transfusion, The Affiliated Hospital, Southwest Medical University, Taiping Road 25#, Jiangyang District, Luzhou, 646000, Sichuan Province, China Department of Transfusion, Zigong Fourth People’s Hospital, Zigong, 643000, China Correspondence to Yuanshuai Huang or Yuhan Wang. The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Below is the link to the electronic supplementary material. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.