title: Engineering polymeric aptamers for selective cytotoxicity.
abstract: Chemotherapy strategies thus far reported can result in both side effects and drug resistance. To address both of these issues at the cellular level, we report a molecular engineering strategy, which employs polymeric aptamers to induce selective cytotoxicity inside target cells. The polymeric aptamers, composed of both multiple cell-based aptamers and a high ratio of dye-labeled short DNA, exploit the target recognition capability of the aptamer, enhanced cell internalization via multivalent effects, and cellular disruption by the polymeric conjugate. Importantly, the polymer backbone built into the conjugate is cytotoxic only inside cells. As a result, selective cytotoxicity is achieved equally in both normal cancer cells and drug-resistant cells. Control assays have confirmed the nontoxicity of the aptamer itself, but they have also shown that the physical properties of the polymer backbone contribute to target cell cytotoxicity. Therefore, our approach may shed new light on drug design and drug delivery.
authors.affiliation: Department of Chemistry, Shands Cancer Center, UF Genetics Institute, University of Florida, Gainesville, Florida 32611-7200, United States.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Meng
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Guizhi
authors.initials: G
authors.lastname: Zhu
authors.forename: Haipeng
authors.initials: H
authors.lastname: Liu
authors.forename: Xiangling
authors.initials: X
authors.lastname: Xiong
authors.forename: Kwame
authors.initials: K
authors.lastname: Sefah
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D052156:SELEX Aptamer Technique / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D011108:Polymers