Cancer cell membrane-camouflaged pH-responsive nanoparticles for enhancing siRNA effect and synergistic anti-tumor therapy Article Swipe

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Jie Zhang , Xia Li , Qi Sun , Yaoqi Wang , Mei Dong , Xiaoling Wang , Yan Su , Yang Tian , Ran Huo , Danni Liu , S Y Liu , Maurício Ribeiro Baldan , Shuang Zhang , Chunying Cui ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-5786929/v1

RNA-based therapies, especially small interfering RNA (siRNA), have attracted extensive attention for tumor treatment. However, most siRNA can’t exert a therapeutic effect due to a lack of targeting to tumor cells and entrapment in lysosomes upon administration. To address the challenges associated with siRNA delivery, a delivery system was developed using zinc oxide nanoparticles (ZnO NPs) coated with cancer cell membranes. ZnO nanoparticles (ZnO NPs) have been recognized as effective pH-responsive nanoparticles and are widely used in the development of drug delivery systems pH-responsive. The ZnO NPs were combined with chitosan to encapsulate siRNA, allowing for dissolution in acidic lysosomes and the subsequent release of siRNA and chitosan complexes. The dissolution of ZnO NPs would also disrupt lysosomes, facilitating the escape of siRNA and enhancing its gene silencing effect. However, the chitosan and ZnO NPs nano-complexes (CS/ZnO@iRNA) were unstable in solution and lacked a specific targeting effect for tumor cells. Thus, a homologous cancer cell membrane was coated onto the nanoparticles, which has been shown to be an effective strategy for enhancing their stability and targeting capabilities. Moreover, ZnO NPs not only dissolve in acidic lysosomes to enhance the efficacy of siRNA but also elevate oxidative stress levels in cells, leading to the induction of cellular apoptosis. It was demonstrated both in vitro and in vivo that the ZnO NPs could synergistically combine with the anti-tumor siRNA (siSurvivin) to inhibit growth of the 4T1 tumor. Altogether, the developed drug delivery system (CCM-CS/ZnO@siSurvivin) offers a new strategy for both enhancing the therapeutic effect of siRNA, while synergistically inhibiting tumor growth.

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Chemistry Cancer Nanoparticle Cancer research Cancer therapy Cell Membrane Cancer treatment Biophysics Nanotechnology Medicine Materials science Biochemistry Internal medicine Biology

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Type: preprint
Language: en
Landing Page: https://doi.org/10.21203/rs.3.rs-5786929/v1
PDF: https://www.researchsquare.com/article/rs-5786929/latest.pdf
OA Status: gold
References: 53
Related Works: 10
OpenAlex ID: https://openalex.org/W4409208353

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DOI: https://doi.org/10.21203/rs.3.rs-5786929/v1

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Title: Cancer cell membrane-camouflaged pH-responsive nanoparticles for enhancing siRNA effect and synergistic anti-tumor therapy

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-04-07

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Authors: Jie Zhang, Xia Li, Qi Sun, Yaoqi Wang, Mei Dong, Xiaoling Wang, Yan Su, Yang Tian, Ran Huo, Danni Liu, S Y Liu, Maurício Ribeiro Baldan, Shuang Zhang, Chunying Cui

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Landing page: https://doi.org/10.21203/rs.3.rs-5786929/v1

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Concepts: Chemistry, Cancer, Nanoparticle, Cancer research, Cancer therapy, Cell, Membrane, Cancer treatment, Biophysics, Nanotechnology, Medicine, Materials science, Biochemistry, Internal medicine, Biology

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