title: Photophysical characterization of anticancer drug valrubicin in rHDL nanoparticles and its use as an imaging agent.
abstract: Nanoparticles are target-specific drug delivery agents that are increasingly used in cancer therapy to enhance bioavailability and to reduce off target toxicity of anti-cancer agents. Valrubicin is an anti-cancer drug, currently approved only for vesicular bladder cancer treatment because of its poor water solubility. On the other hand, valrubicin carrying reconstituted high density lipoprotein (rHDL) nanoparticles appear ideally suited for extended applications, including systemic cancer chemotherapy. We determined selected fluorescence properties of the free (unencapsulated) drug vs. valrubicin incorporated into rHDL nanoparticles. We have found that upon encapsulation into rHDL nanoparticles the quantum yield of valrubicin fluorescence increased six fold while its fluorescence lifetime increased about 2 fold. Accordingly, these and potassium iodide (KI) quenching data suggest that upon incorporation, valrubicin is localized deep in the interior of the nanoparticle, inside the lipid matrix. Fluorescence anisotropy of the rHDL valrubicin nanoparticles was also found to be high along with extended rotational correlation time. The fluorescence of valrubicin could also be utilized to assess its distribution upon delivery to prostate cancer (PC3) cells. Overall the fluorescence properties of the rHDL: valrubicin complex reveal valuable novel characteristics of this drug delivery vehicle that may be particularly applicable when used in systemic (intravenous) therapy.
authors.affiliation: Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, UNT Health Science Center, Fort Worth, TX, USA. Electronic address: sunilajit.shah@live.unthsc.edu.
authors.forename: Sunil
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, UNT Health Science Center, Fort Worth, TX, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Chib
authors.affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX, USA.
authors.forename: Sangram
authors.initials: S
authors.lastname: Raut
authors.affiliation: Cell Biology and Immunology, North Texas Eye Research Institute, UNT Health Science Center, Fort Worth, TX, USA.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Bermudez
authors.affiliation: Department of Integrative Physiology and Anatomy, UNT Health Science Center, Fort Worth, TX, USA.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Sabnis
authors.affiliation: Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, UNT Health Science Center, Fort Worth, TX, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Duggal
authors.affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Kimball
authors.affiliation: Department of Integrative Physiology and Anatomy, UNT Health Science Center, Fort Worth, TX, USA.
authors.forename: Andras G
authors.initials: AG
authors.lastname: Lacko
authors.affiliation: Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, UNT Health Science Center, Fort Worth, TX, USA; Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX, USA.
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Gryczynski
authors.affiliation: Department of Cell Biology and Immunology, Center for Fluorescence Technologies and Nanomedicine, UNT Health Science Center, Fort Worth, TX, USA. Electronic address: ignacy.gryczynski@unthsc.edu.
authors.forename: Ignacy
authors.initials: I
authors.lastname: Gryczynski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D016632:Apolipoprotein A-I; D003287:Contrast Media; D008075:Lipoproteins, HDL; C016163:valrubicin; D004317:Doxorubicin
keywords: Cancer; Confocal imaging; Fluorescence spectroscopy; Valrubicin; rHDL nanoparticles