title: Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro.
abstract: Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the non-specific toxicity of chemotherapy by selectively directing anticancer drugs to tumor cells. MUC1 protein is an attractive target for tumor-specific drug delivery owning to its overexpression in most adenocarcinomas. In this study, a novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin (Dox) to cancer cells. We developed an 86-base DNA aptamer (MA3) that bound to a peptide epitope of MUC1 with a K(d) of 38.3 nM and minimal cross reactivity to albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing models, MA3 was found to preferentially bind to MUC1-positive but not MUC1-negative cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found capable of carrying doxorubicin into MUC1-positive tumor cells, while significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox retained the efficacy of doxorubicin against MUC1-positive tumor cells, but lowered the toxicity to MUC1-negative cells (P<0.01). The results suggest that the MUC1 aptamer may have potential utility as a targeting ligand for selective delivery of cytotoxic agent to MUC1-expressing tumors.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Jinhong
authors.initials: J
authors.lastname: Duan
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.forename: Fengdan
authors.initials: F
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Xian-Da
authors.initials: XD
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D052158:Aptamers, Peptide / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D015195:Drug Design; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D015233:Models, Statistical; D018396:Mucin-1 / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D052158:Aptamers, Peptide; C060192:MUC1 protein, human; D018396:Mucin-1; D034741:RNA, Small Interfering; D004317:Doxorubicin