Folate Receptor-Targeted Aggregation-Enhanced Near-IR Emitting Silica Nanoprobe for One-Photon in Vivo and Two-Photon ex Vivo Fluorescence Bioimaging

    Authors

    X. H. Wang; A. R. Morales; T. Urakami; L. F. Zhang; M. V. Bondar; M. Komatsu;K. D. Belfield

    Comments

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    Abbreviated Journal Title

    Bioconjugate Chem.

    Keywords

    CANCER-CELLS; ORGANIC NANOPARTICLES; INFLAMMATORY DISEASES; INDUCED; EMISSION; GENE DELIVERY; QUANTUM DOTS; MICROSCOPY; THERAPY; PROBES; DRUG; Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic

    Abstract

    A two-photon absorbing (2PA) and aggregation-enhanced near-infrared (MR) emitting pyran derivative, encapsulated in and stabilized by silica nanopartides (SiNPs), is reported as a nanoprobe for two-photon fluorescence microscopy (2PFM) bioimaging that overcomes the fluorescence quenching associated with high chromophore loading. The new SiNP probe exhibited aggregate-enhanced emission producing nearly twice as strong a signal as the unaggregated dye, a 3-fold increase in two-photon absorption relative to the DFP in solution, and approximately 4-fold increase in photostability. The surface of the nanoparticles was functionalized with a folic acid (FA) derivative for folate-mediated delivery of the nanoprobe for 2PFM bioimaging. Surface modification of SiNPs with the FA derivative was supported by zeta potential variation and H-1 NMR spectral characterization of the SiNPs as a function of surface modification. In vitro studies using HeLa cells expressing a folate receptor (FR) indicated specific cellular uptake of the functionalized nanopartides. The nanoprobe was demonstrated for FR-targeted one-photon in vivo imaging of HeLa tumor xenograft in mice upon intravenous injection of the probe. The FR-targeting nanoprobe not only exhibited highly selective tumor targeting but also readily extravasated from tumor vessels, penetrated into the tumor parenchyma, and was internalized by the tumor cells. Two-photon fluorescence microscopy bioimaging provided three-dimensional (3D) cellular-level resolution imaging up to 350 mu m deep in the HeLa tumor.

    Journal Title

    Bioconjugate Chemistry

    Volume

    22

    Issue/Number

    7

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    1438

    Last Page

    1450

    WOS Identifier

    WOS:000292893100023

    ISSN

    1043-1802

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