title: Targeted delivery of doxorubicin using a colorectal cancer-specific ssDNA aptamer.
abstract: Targeted drug delivery is particularly important in cancer treatment because many antitumor drugs are nonspecific and highly toxic to both cancerous and normal cells. The L33 aptamer is a single-stranded DNA (ssDNA) sequence that has the ability to recognize human colorectal cancer (CRC) cell line HCT116 specifically. In this study, we demonstrated that the L33 aptamer can selectively internalize into target HCT116 cells via receptor-mediated endocytosis. Based on this finding, we developed an aptamer-based drug delivery system using L33 as the carrier of the antitumor drug doxorubicin (Dox). The L33-Dox complex exhibited specific and high affinity (Kd  = 14.3 ± 2.2 nM) binding to HCT116 cells. The results of cytotoxicity assays revealed that the L33-Dox complex was capable of selectively delivering the drug to the target HCT116 cells and lowered the toxicity for nontarget CL187 cells. These findings indicate that the aptamer-based targeted drug delivery system has the potential to be used in clinical settings and may overcome drug resistance to a certain extent because high drug dosages can be directed toward target cells.
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Shenyang, 110001, China; Department of Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, 110001, China.
authors.forename: Wanming
authors.initials: W
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Jin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004277:DNA, Single-Stranded / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D004277:DNA, Single-Stranded; D004337:Drug Carriers; D004317:Doxorubicin
keywords: aptamer; colorectal cancer; doxorubicin; drug delivery; targeted therapy