A pH-responsive silica-metal-organic framework hybrid nanoparticle for the delivery of hydrophilic drugs, nucleic acids, and CRISPR-Cas9 genome-editing machineries

JOURNAL OF CONTROLLED RELEASE

卷:324

Article

Wang, Yuyuan^1,2  Shahi, Pawan K.³  Xie, Ruosen^2,4  Zhang, Huilong⁵  Abdeen, Amr A.²  Yodsanit, Nisakorn^1,2  Ma, Zhenqiang⁵  Saha, Krishanu^1,2  Pattnaik, Bikash R.^3,6,7  Gong, Shaoqin^1,2,4,6,8 

[1] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53715 USA

[2] Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI 53715 USA

[3] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA

[4] Univ Wisconsin, Dept Mat Sci & Engn, Madison, WI 53706 USA

[5] Univ Wisconsin, Dept Elect & Comp Engn, Madison, WI 53706 USA

[6] Univ Wisconsin, McPherson Eye Res Inst, Madison, WI 53705 USA

[7] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA

[8] Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA

关键词: Silica;    Metal-organic framework;    Hybrid nanoparticle;    Gene delivery;    Genome editing machinery delivery;   

DOI  :  10.1016/j.jconrel.2020.04.052

来源: Elsevier

【 摘 要 】

Efficient delivery of hydrophilic drugs, nucleic acids, proteins, and any combination thereof is essential for various biomedical applications. Herein, we report a straightforward, yet versatile approach to efficiently encapsulate and deliver various hydrophilic payloads using a pH-responsive silica-metal-organic framework hybrid nanoparticle (SMOF NP) consisting of both silica and zeolitic imidazole framework (ZIF). This unique SMOF NP offers a high loading content and efficiency, excellent stability, and robust intracellular delivery of a variety of payloads, including hydrophilic small molecule drugs (e.g., doxorubicin hydrochloride), nucleic acids (e.g., DNA and mRNA), and genome-editing machineries (e.g., Cas9-sgRNA ribonucleoprotein (RNP), and RNP together with donor DNA (e.g., RNP + ssODN)). The superior drug delivery/gene transfection/genome-editing efficiencies of the SMOF NP are attributed to its pH-controlled release and endosomal escape capabilities due to the proton sponge effect enabled by the imidazole moieties in the SMOF NPs. Moreover, the surface of the SMOF NP can be easily customized (e.g., PEGylation and ligand conjugation) via various functional groups incorporated into the silica component. RNP-loaded SMOF NPs induced efficient genome editing in vivo in murine retinal pigment epithelium (RPE) tissue via subretinal injection, providing a highly promising nanoplatform for the delivery of a wide range of hydrophilic payloads.

【 授权许可】

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