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Lookup NU author(s): Nga Vo, Dr Lei HuangORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 Zhang et al. Purpose: In order to overcome the biological barriers at all levels and enhance the delivery efficiency of siRNA, we have prepared a multifunctional siRNA delivery system (CHCE/siRNA nanoparticles) through self-assembly of the carboxymethyl chitosan modified with histidine, cholesterol, and anti-EGFR antibody (CHCE). Methods: The morphology of CHCE/siRNA NPs was detected by dynamic light scattering and scanning electron microscope. In vitro, we assessed the tumor-targeting, cellular uptake, and endosomal escape by flow cytometry and confocal laser scanning microscopy, confirming the CHCE/siRNA NPs functions in gene silencing and cell killing ability. In vivo, we examined the biodistribution of the CHCE/siRNA NPs by the IVIS imaging system and confirmed the therapeutic effect of NPs in the nude-mouse tumor model. Results: The CHCE/siRNA NPs exhibited nanosized spherical with narrow size distribution. In vitro, the CHCE/siRNA NPs incorporated a dual capability of tumor targeting and pH response that could facilitate cellular bind, cellular uptake, and endosomal escape. The CHCE/siRNA NPs could effectively silence the vascular endothelial growth factor A (VEGFA) to cause cell apoptosis and inhibit proliferation. In vivo, the CHCE/siRNA NPs could target tumor sites to knock down VEGFA and achieve a better anti-tumor effect. Conclusion: We successfully prepared a novel siRNA delivery system with the double capability of tumor targeting and pH response, which can break through the biological barriers to penetrate deep into tumors and achieve better therapeutic tumor effects, providing a new ideal delivery platform for siRNA.
Author(s): Zhang X, Qin B, Wang M, Feng J, Zhang C, Zhu C, He S, Liu H, Wang Y, Averick SE, Vo NTN, Huang L, Liu W, Wang Z
Publication type: Article
Publication status: Published
Journal: International Journal of Nanomedicine
Year: 2022
Volume: 17
Pages: 953-967
Online publication date: 05/03/2022
Acceptance date: 18/02/2022
Date deposited: 28/03/2022
ISSN (electronic): 1178-2013
Publisher: Dove Press Ltd
URL: https://doi.org/10.2147/IJN.S340926
DOI: 10.2147/IJN.S340926
PubMed id: 35280336
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