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Self-assembled aptamer-based drug carriers for bispecific cytotoxicity to cancer cells.

Authors
  • Zhu, Guizhi
  • Meng, Ling
  • Ye, Mao
  • Yang, Liu
  • Sefah, Kwame
  • O'Donoghue, Meghan B
  • Chen, Yan
  • Xiong, Xiangling
  • Huang, Jin
  • Song, Erqun
  • Tan, Weihong
Type
Published Article
Journal
Chemistry - An Asian Journal
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jun 01, 2012
Volume
7
Issue
7
Pages
1630–1636
Identifiers
DOI: 10.1002/asia.201101060
PMID: 22492537
Source
Medline
License
Unknown

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.

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