title: Self-assembled aptamer-based drug carriers for bispecific cytotoxicity to cancer cells.
abstract: Monovalent aptamers can deliver drugs to target cells by specific recognition. However, different cancer subtypes are distinguished by heterogeneous biomarkers and one single aptamer is unable to recognize all clinical samples from different patients with even the same type of cancers. To address heterogeneity among cancer subtypes for targeted drug delivery, as a model, we developed a drug carrier with a broader recognition range of cancer subtypes. This carrier, sgc8c-sgd5a (SD), was self-assembled from two modified monovalent aptamers. It showed bispecific recognition abilities to target cells in cell mixtures; thus broadening the recognition capabilities of its parent aptamers. The self-assembly of SD simultaneously formed multiple drug loading sites for the anticancer drug doxorubicin (Dox). The Dox-loaded SD (SD-Dox) also showed bispecific abilities for target cell binding and drug delivery. Most importantly, SD-Dox induced bispecific cytotoxicity in target cells in cell mixtures. Therefore, by broadening the otherwise limited recognition capabilities of monovalent aptamers, bispecific aptamer-based drug carriers would facilitate aptamer applications for clinically heterogeneous cancer subtypes that respond to the same cancer therapy.
authors.affiliation: Department of Chemistry, Shands Cancer Center, UF Genetics Institute, University of Florida, Gainesville, Florida 32611-7200, USA.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Zhu
authors.forename: Ling
authors.initials: L
authors.lastname: Meng
authors.forename: Mao
authors.initials: M
authors.lastname: Ye
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Kwame
authors.initials: K
authors.lastname: Sefah
authors.forename: Meghan B
authors.initials: MB
authors.lastname: O'Donoghue
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiangling
authors.initials: X
authors.lastname: Xiong
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D004317:Doxorubicin