title: Polymer-drug conjugates for intracellar molecule-targeted photoinduced inactivation of protein and growth inhibition of cancer cells.
abstract: For most molecule-targeted anticancer systems, intracellular protein targets are very difficult to be accessed by antibodies, and also most efforts are made to inhibit protein activity temporarily rather than inactivate them permanently. In this work we firstly designed and synthesized multifunctional polymer-drug conjugates (polythiophene-tamoxifen) for intracellular molecule-targeted binding and inactivation of protein (estrogen receptor α, ERα) for growth inhibition of MCF-7 cancer cells. Small molecule drug was conjugated to polymer side chain for intracellular signal protein targeting, and simultaneously the fluorescent characteristic of polymer for tracing the cellular uptake and localization of polythiophene-drug conjugates by cell imaging. Under light irradiation, the conjugated polymer can sensitize oxygen to produce reactive oxygen species (ROS) that specifically inactivate the targeted protein, and thus inhibit the growth of tumor cells. The conjugates showed selective growth inhibition of ERα positive cancer cells, which exhibits low side effect for our intracellular molecule-targeted therapy system.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Huanxiang
authors.initials: H
authors.lastname: Yuan
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Fengting
authors.initials: F
authors.lastname: Lv
authors.forename: Libing
authors.initials: L
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D011108:Polymers / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D047628:Estrogen Receptor alpha; D011108:Polymers; D017382:Reactive Oxygen Species; D013876:Thiophenes; D013629:Tamoxifen; C066730:polythiophene