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A one-pot modular assembly strategy for triple-play enhanced cytosolic siRNA delivery

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Abstract

Robust efficiency for cytosolic small interfering RNA (siRNA) delivery is of great importance for effective gene therapy. To significantly improve the cytosolic siRNA delivery, a “one-pot modular assembly” strategy is developed to assemble a triple-play enhanced cytosolic siRNA delivery system via a facile and innocuous copper-free click reaction. Specifically, three modules are prepared including octreotide for receptor-mediated endocytosis, a cell-penetrating peptide (CPP) for cell penetration, and glutamic acid for the charge-reversal property. All three modules with distinct facilitating endocytosis effects are expediently assembled on the surface of the siRNA/liposome complex to fabricate a multifunctional integrated siRNA delivery system (OCA-CC). OCA-CC has been demonstrated to have enhanced cytosolic delivery and superior gene-silencing efficiency in multiple tumor cells due to the combined effects of all the three modules. High levels of survivin-silencing are also achieved by OCA-CC on orthotopic human breast cancer (MCF-7)-bearing mice accompanied by significant tumor inhibition. This research provides a facile strategy to produce safe and tunable siRNA delivery systems for effective gene therapy and to facilitate the development of multifunctional siRNA vectors.

Graphical abstract: A one-pot modular assembly strategy for triple-play enhanced cytosolic siRNA delivery

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Publication details

The article was received on 12 Nov 2018, accepted on 11 Dec 2018 and first published on 12 Dec 2018


Article type: Paper
DOI: 10.1039/C8BM01454J
Citation: Biomater. Sci., 2019, Advance Article

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    A one-pot modular assembly strategy for triple-play enhanced cytosolic siRNA delivery

    D. Xie, J. Du, M. Bao, A. Zhou, C. Tian, L. Xue, C. Ju, J. Shen and C. Zhang, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C8BM01454J

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