Cellular uptake and cytotoxicity of drug-peptide conjugates regulated by conjugation site

Pengcheng Zhang, Andrew G. Cheetham, Lye Lin Lock, Honggang Cui

Research output: Contribution to journalArticlepeer-review


Conjugation of anticancer drugs to hydrophilic peptides such as Tat is a widely adopted strategy to improve the drug's solubility, cellular uptake, and potency against cancerous cells. Here we report that attachment of an anticancer drug doxorubicin to the N-or C-terminal of the Tat peptide can have a significant impact on their cellular uptake and cytotoxicity against both drug-sensitive and drug-resistant cancer cells. We observed higher cellular uptake by both cell lines for C-terminal conjugate relative to the N-terminal analogue. Our results reveal that the C-terminal conjugate partially overcame the multidrug resistance of cervical cancer cells, while the N-terminal conjugate showed no significant improvement in cytotoxicity when compared with free doxorubicin. We also found that both N-and C-conjugates offer a mechanism to circumvent drug efflux associated with multidrug resistance.

Original languageEnglish (US)
Pages (from-to)604-613
Number of pages10
JournalBioconjugate Chemistry
Issue number4
StatePublished - Apr 17 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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