title: Modular Integration of Upconverting Nanocrystal-Dendrimer Composites for Folate Receptor-Specific NIR Imaging and Light-Triggered Drug Release.
abstract: Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Pamela T
authors.initials: PT
authors.lastname: Wong
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Chen
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Shengzhuang
authors.initials: S
authors.lastname: Tang
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Yanik
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Payne
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Jhindan
authors.initials: J
authors.lastname: Mukherjee
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Coulter
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Kenny
authors.initials: K
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Seok Ki
authors.initials: SK
authors.lastname: Choi
mesh_terms: D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D004705:Endocytosis; D005434:Flow Cytometry; D058975:Folate Receptor 1 / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D008027:Light; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D019265:Spectroscopy, Near-Infrared
chemical_list: D050091:Dendrimers; D058975:Folate Receptor 1; D004317:Doxorubicin; D005492:Folic Acid
keywords: NIR detection; PAMAM dendrimers; folate receptors; imaging; nanocrystals; photocaged doxorubicin; upconversion