Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro

• Published in: PloS one Vol. 7; no. 2; p. e31970
• Main Authors: Hu, Yan, Duan, Jinhong, Zhan, Qimin, Wang, Fengdan, Lu, Xin, Yang, Xian-Da
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22-02-2012; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma - metabolism; Albumin; Amino Acids - chemistry; Anthracyclines; Antigenic determinants; Antigens; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Antitumor agents; Aptamers; Aptamers, Peptide - chemistry; Biology; Breast cancer; Cancer; Cancer cells; Cancer therapies; Care and treatment; Cell Line, Tumor; Cell Survival; Chemotherapy; Cytotoxic agents; Cytotoxicity; Deoxyribonucleic acid; Development and progression; DNA; DNA structure; Doxorubicin; Doxorubicin - pharmacology; Drug delivery; Drug Delivery Systems; Drug Design; Drugs; Epitopes; Flow Cytometry - methods; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Kinetics; Ligands; Liver cancer; Lung cancer; Lung diseases; Medicine; Models, Statistical; Mucin-1 - metabolism; Mucins; Nanoparticles; Peptides; Prostate cancer; Protein Binding; Proteins; RNA, Small Interfering - metabolism; Targeted cancer therapy; Toxicity; Tumor cells; Tumors; Tianjin China; Beijing China; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0031970

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.