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.
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