title: In vitro evaluation of HPMA-copolymers targeted to HER2 expressing pancreatic tumor cells for image guided drug delivery.
abstract: Personalized medicine for the treatment of pancreatic cancer is one potential avenue which can prevent the dire outcome of this difficult to treat disease. Image guided drug delivery (IGDD) is a method allowing real-time imaging of drug therapy in order to predict the potential efficacy and safety of a given treatment. Water soluble macromolecular drug carriers such as N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers provide multifunctional platforms for the construction of such IGDD systems. HPMA copolymer conjugates containing gemcitabine, a targeting ligand for HER2 receptors overexpressed in some pancreatic cancers, and an (111) In(3+) chelating agent are synthesized, characterized, and evaluated in vitro for their potential use as an IGDD system for pancreatic tumors. The conjugates are capable of binding to pancreatic tumor cell lines which express HER2. In vitro drug release is achieved under physiological and acidic pH environments. The chelated radioisotopes are stable in the presence of mouse serum. The conjugates are effective in killing pancreatic tumor cell lines in vitro. These copolymers have potential for further preclinical evaluation in pancreatic tumor models.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, Utah Center for Nanomedicine, Nano Institute of Utah University of Utah, 36 S Wasatch Dr., SMBB 5515, Salt Lake City, UT, 84112, USA; Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Buckway
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Wang
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007205:Indium Radioisotopes / Q000737:chemistry; D020128:Inhibitory Concentration 50; D051379:Mice; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D000178:Acrylamides; D003841:Deoxycytidine; D004337:Drug Carriers; D007205:Indium Radioisotopes; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; D000093542:Gemcitabine; C508053:ERBB2 protein, human; C032976:N-(2-hydroxypropyl)methacrylamide
keywords: copolymers; gemcitabine; imaging; pancreatic cancer