title: Aptamer-mediated delivery of chemotherapy to pancreatic cancer cells.
abstract: Gemcitabine is a nucleoside analog that is currently the best available single-agent chemotherapeutic drug for pancreatic cancer. However, efficacy is limited by our inability to deliver sufficient active metabolite into cancer cells without toxic effects on normal tissues. Targeted delivery of gemcitabine into cancer cells could maximize effectiveness and concurrently minimize toxic side effects by reducing uptake into normal cells. Most pancreatic cancers overexpress epidermal growth factor receptor (EGFR), a trans-membrane receptor tyrosine kinase. We utilized a nuclease resistant RNA aptamer that binds and is internalized by EGFR on pancreatic cancer cells to deliver gemcitabine-containing polymers into EGFR-expressing cells and inhibit cell proliferation in vitro. This approach to cell type-specific therapy can be adapted to other targets and to other types of therapeutic cargo.
authors.affiliation: Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Partha
authors.initials: P
authors.lastname: Ray
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Cheek
authors.forename: Mariam L
authors.initials: ML
authors.lastname: Sharaf
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Ellington
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Sullenger
authors.forename: Barbara Ramsay
authors.initials: BR
authors.lastname: Shaw
authors.forename: Rebekah R
authors.initials: RR
authors.lastname: White
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms; D013194:Staining and Labeling; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D005456:Fluorescent Dyes; D003841:Deoxycytidine; D066246:ErbB Receptors; D000093542:Gemcitabine