title: Intracellular fate of polymer therapeutics investigated by fluorescence lifetime imaging and fluorescence pattern analysis.
abstract: Nanocarriers bearing anticancer drugs are promising candidates to improve the efficacy of cancer therapy and minimize side effects. The most potent cytostatics used in the treatment of various cancers are anthracyclines, e.g. doxorubicin or pirarubicin. Recently, polymer therapeutics carrying anthracyclines have been intensively studied. The precise characterization of in vitro nanocarrier biological behavior brings a better understanding of the nanocarrier characteristics and enables prediction of the behavior of the nanocarrier during in vivo application. Advanced fluorescence detection methods, e.g. fluorescence lifetime imaging microscopy (FLIM), were successfully exploited to describe the properties of various polymeric nano-systems and contributed to a complex view of anthracyclines' intracellular transport and DNA intercalation. Here, we report the application of a specific technique for processing FLIM images, called fluorescence pattern decomposition, to evaluate early events after doxorubicin or pirarubicin treatment of cells. Moreover, we characterized changes in the intracellular localization and release of the anthracyclines during the incubation of cells with polymer nanotherapeutics based on poly[N-(2-hydroxypropyl)-methacrylamide] (pHPMA).
authors.affiliation: Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, Czech Republic. janouskova@imc.cas.cz.
authors.forename: J
authors.initials: J
authors.lastname: Panek
authors.forename: E
authors.initials: E
authors.lastname: Koziolova
authors.forename: P
authors.initials: P
authors.lastname: Stepanek
authors.forename: T
authors.initials: T
authors.lastname: Etrych
authors.forename: O
authors.initials: O
authors.lastname: Janouskova
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004337:Drug Carriers; D006801:Humans; D053758:Nanoparticles; D061848:Optical Imaging / Q000379:methods*; D011108:Polymers
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin; C027260:pirarubicin