NIR-induced spatiotemporally controlled gene silencing by upconversion nanoparticle-based siRNA nanocarrier

JOURNAL OF CONTROLLED RELEASE

卷:282

Article; Proceedings Paper

Chen, Guojun^1,2  Ma, Ben^2,3  Xie, Ruosen^1,2  Wang, Yuyuan^1,2  Dou, Kefeng³  Gong, Shaoqin^1,2,4 

[1] Univ Wisconsin, Dept Mat Sci & Engn, Madison, WI 53715 USA

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

[3] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China

[4] Univ Wisconsin, Dept Chem, Madison, WI 53715 USA

关键词: Spatiotemporally controlled gene silencing;    NIR-controlled release;    Upconversion nanoparticle;    Host-guest interaction;   

DOI  :  10.1016/j.jconrel.2017.12.028

来源: Elsevier

【 摘 要 】

Spatiotemporal control over the release or activation of biomacromolecules such as siRNA remains a significant challenge. Light-controlled release has gained popularity in recent years; however, a major limitation is that most photoactivable compounds/systems respond only to UV irradiation, but not near-infrared (NIR) light that offers a deeper tissue penetration depth and better biocompatibility. This paper reports a simple NIR-to-UV upconversion nanoparticle (UCNP)-based siRNA nanocarrier for NIR-controlled gene silencing. siRNA is complexed onto a NaYF4:Yb/Tm/Er UCNP through an azobenzene (Azo)-cyclodextrin (CD) host-guest interaction. The UV emission generated by the NIR-activated UCNP effectively triggers the trans-to-cis photoisomerization of azobenzene, thus leading to the release of siRNA due to unmatched host - guest pairs. The UCNP-siRNA complexes are also functionalized with PEG (i.e., UCNP-(CD/Azo)-siRNA/PEG NPs), targeting ligands (i.e., EGFR-specific GE11 peptide), acid-activatable cell-penetrating peptides (i.e., TH peptide), and imaging probes (i.e., Cy5 fluorophore). The UCNP-(CD/Azo)-siRNA/PEG NPs with both GE11 and TH peptides display a high level of cellular uptake and an excellent endosomal/lysosomal escape capability. More importantly, NIR-controlled spatiotemporal knockdown of GFP expression is successfully achieved in both a 2D monolayer cell model and a 3D multicellular tumor spheroid model. Thus, this simple and versatile nanoplatform has great potential for the selective activation or release of various biomacromolecules.

【 授权许可】

Free