title: Passive Tumor Targeting of Polymer Therapeutics: In Vivo Imaging of Both the Polymer Carrier and the Enzymatically Cleavable Drug Model.
abstract: The enzymatic release of a model drug from a polymer carrier inside a tumor using multispectral optical imaging in vivo in nude mice bearing colorectal carcinomas HT-29 and DLD-1 is demonstrated. Much higher release rate in vivo from a linear (30 kDa) (N-2-hydroxypropyl)methacrylamide-based polymer compared with a high molecular weight branched (170 kDa) polymer conjugate is observed, probably due to steric hindrance of the cleavable spacer of the latter polymer to proteolytic enzymes. There is no significant difference in the relative biodistribution of the two polymers, but the branched polymer circulates much longer. Both polymers are labeled with two different fluorophores. Dyomics-676 as a drug model is attached to the polymer via an enzymatically cleavable Gly-Phe-Leu-Gly spacer; Dyomics 782 is bound to the same polymer via a nondegradable amide bond, enabling the tracking of the polymer carrier after i.v. application to mice.
authors.affiliation: Department of Biomedical Polymers, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 2, 162 06, Prague, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Pola
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology, and Biopharmacy, Martin Luther University Halle-Wittenberg, 06120, Halle, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Heinrich
authors.affiliation: Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120, Halle, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.affiliation: Department of Biomedical Polymers, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 2, 162 06, Prague, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Kostka
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology, and Biopharmacy, Martin Luther University Halle-Wittenberg, 06120, Halle, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
authors.affiliation: Department of Biomedical Polymers, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 2, 162 06, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Pechar
authors.affiliation: Department of Biomedical Polymers, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq. 2, 162 06, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Etrych
mesh_terms: D000178:Acrylamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D004337:Drug Carriers; D005456:Fluorescent Dyes; C032976:N-(2-hydroxypropyl)methacrylamide
keywords: EPR effect; enzymatic release; in vivo imaging; polymer drug carriers; tumor targeting