USE OF UPCONVERSION FLUORESCENT NANOPARTICLES FOR IMAGING AND PHOTO-CONTROLLED GENE THERAPY

Abstract

Light-controlled gene delivery and imaging in deeper tissues is hindered by poor penetration of visible light or damaging effects of UV light. Upconversion nanoparticles (UCNPs) can overcome these hurdles by converting safe near-infrared (NIR) light to ultraviolet (UV, to uncage genes) and/or visible light (to release reactive oxygen species for endosomal escape) and/or NIR light (to image) both in vitro and in vivo. In this project, core-shell upconversion nanoparticles with tunable UV-Visible-NIR spectrum were synthesized, and surface modified with dendrimer polyamidoamine (PAMAM) via ligand exchange (PAMAM-UNCP). PAMAM-UCNPs were co-loaded with caged nucleic acids (plasmid GFP DNA, ERα siRNA) and photosensitizer TPPS2a. Caging was done by covalently attaching 6-bromo-4-diazomethyl-7-hydroxycoumarin to nucleic acids. When administered to MCF-7 cancer model in vitro, PAMAM-UCNP-caged-nucleic-acid-TPPS2a complex was able to control gene expression/silencing via photoactivation of caged DNA/siRNA and TPPS2a. Simultaneously, background free imaging was also done. The results indicate UCNPs have the potential as a controlled, safe and convenient tool in gene therapy and imaging of many conditions.