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Multilevel chitosan–gelatin particles loaded with P4HA1 siRNA suppress glioma development

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Abstract

It has been reported that prolyl 4-hydroxylase subunit alpha 1 (P4HA1) promoted tumor growth and metastasis of glioma; thus, targeting P4HA1 may be a promising therapeutic strategy against glioma. In consideration of the instability of siRNA in vivo, the chitosan–gelatin microspheres loaded with P4HA1 siRNA (P4HA1 siRNA@CGM) were employed. Firstly, the gel electrophoresis and hemolytic test were performed to assess the stability and blood compatibility of P4HA1 siRNA@CGM. Then, methyl thiazolyl tetrazolium (MTT), cell colony formation, Transwell assay, wound healing assay, gliosphere formation, tube formation, and Western blot were performed to assess the effects of P4HA1 siRNA@CGM on the biological functions of glioma. Finally, 125I-labeled P4HA1 siRNA@CGM was injected into the xenograft mice, radionuclide imaging was recorded, Ki67 and terminal deoxynucleoitidyl transferase–mediated nick end labeling (TUNEL) staining was performed to assess the effects of P4HA1 siRNA@CGM on tumor growth and apoptosis of glioma in vivo. The results showed that P4HA1 siRNA and P4HA1 siRNA@CGM not only markedly inhibited the proliferation, metastasis, gliosphere formation, and the protein levels of interstitial markers (N-cadherin and vimentin) and the transcription factors of epithelial–mesenchymal transition (EMT) (Snail, Slug, and Twist1) in glioma cells, but also inhibited the tube formation in human brain microvascular endothelial cells (HBMECs), and P4HA1 siRNA@CGM exhibited the better inhibitory effects than P4HA1 siRNA. Above results suggested the feasibility of P4HA1 siRNA@CGM in the clinical treatment of glioma.

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Funding

This work was supported by National Natural Science Foundation of China (No. 82071381).

Author information

Author notes

  1. Yiting Zhou and Jiajia Tian contributed equally to this work.

Authors and Affiliations

  1. Department of Intervention Therapy, The Affiliated Hospital of Jiangnan University, Wuxi, 214002, China

    Yiting Zhou

  2. Department of Neurosurgery, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, 214000, China

    Jiajia Tian

  3. Department of Neurosurgery, Medical School of Nantong University, Nantong University, Nantong, 226019, China

    Yi Zhu & Yating Zhang

  4. Department of Neurosurgery, Wuxi No. 2 People’s Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, 214002, China

    Yi Zhu & Yating Zhang

  5. Department of Neurosurgery, Jiangnan University Medical Center, Wuxi, 214005, China

    Xudong Zhao

  6. Department of Neurosurgery, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, 214002, China

    Xudong Zhao

  7. Wuxi Neurosurgical Institute, Wuxi, 214002, China

    Xudong Zhao

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  1. Yiting Zhou
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Contributions

Yiting Zhou and Jiajia Tian contributed equally to this work. Y.Zhou and J.Tian designed the research and drafted the manuscript. All authors participated in the experiments and analysis of data. All authors read and approved the final manuscript.

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Correspondence to Xudong Zhao.

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Zhou, Y., Tian, J., Zhu, Y. et al. Multilevel chitosan–gelatin particles loaded with P4HA1 siRNA suppress glioma development. Drug Deliv. and Transl. Res. 14, 665–677 (2024). https://doi.org/10.1007/s13346-023-01422-8

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  • DOI: https://doi.org/10.1007/s13346-023-01422-8

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