Abstract LB-102: Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy

Purpose: Nanoparticle based drug delivery systems have shown promising applications in cancer treatments. Among various nanoparticles, upconversion nanoparticles (UCNPs) allow for the conversion of near infrared (NIR) excitation to localized UV/visible emission providing unprecedented control over UCNP based delivery platforms for deep tissue therapeutic payload release, both spatially and temporally. This study reports the layer-by-layer engineering of UCNP based siRNA and miRNA delivery systems for application in cancer therapy. Experimental Design: To obtain the nanoparticle core, NaYF4:Yb,Er UCNPs were synthesized via thermal decomposition method. The morphology and size of the UCNPs were assessed by transmission electron microscopic (TEM). The upconversion fluorescence property was studied by fluorescence spectroscopy using a 980 nm laser as the excitation source. To enable gene delivery, the naked UCNPs were then surface functionalized with biocompatible polymers using polyacrylic acid (PAA) and poly allylamine hydrochloride (PAH). Surface functionalization was accomplished through layer-by-layer assembly of polyelectrolyte multilayers. Successful surface functionalization was demonstrated by measuring zeta potential after assembly of each layer. Biocompatibility of the developed delivery system was tested by MTT assay. Gel electrophoresis was employed to determine the loading capacity of the delivery system. We then tested the siRNA, miRNA, and EGFP expression vector transfection efficiency in different cancer cell lines. Results: The diameter of the synthesized UCNPs was ∼40 nm. Upon 980 nm excitation, green emission and red emission were identified from the fluorescence spectrum. Zeta potential of the delivery system was ∼+38 mV, indicating its capability to absorb negatively charged siRNA, miRNA, or EGFP vector by electrostatic interaction. The MTT assay demonstrated good biocompatibility. Significant retardation of siRNA, miRNA, or EGFP plasmid in gel electrophoresis assay was observed when mixed with PAA and PAH coated UCNPs. In contrast, UCNP-PAA without PAH coating did not retard siRNA, miRNA, or EGFP plasmid. Confocal laser scanning microscopy results provided direct evidence of siRNA, miRNA, or EGFP plasmid transfection. Conclusions: In this proof-of-concept study, a layer-by-layer engineered UCNP based siRNA and miRNA delivery system was successfully developed. Our novel delivery system opens up preparation of advanced UCNP based photoresponsive delivery systems that allow remote, precise, and trackable control over therapeutic payload (e.g., drug, gene) release for better cancer theranostics. Citation Format: Lin Min, YAN GAO, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan. Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-102. doi:10.1158/1538-7445.AM2015-LB-102