Investigation of the drug binding properties and cytotoxicity of DNA-capped nanoparticles designed as delivery vehicles for the anticancer agents doxorubicin and actinomycin D

Colleen M. Alexander, James C. Dabrowiak, Mathew M Maye

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Oligonucleotide-functionalized gold nanoparticles (AuNP) were designed and synthesized to be delivery vehicles for the clinically used anticancer drugs doxorubicin (DOX) and actinomycin D (ActD). Each vehicle contains a tailorable number of DNA duplexes, each possessing three high-affinity sequences for the intercalation of either DOX or ActD, thus allowing for control of drug loading. Drug binding was evaluated by measuring changes to DNA melting temperature, Tm, hydrodynamic diameter, Dh, and surface plasmon resonance wavelength, λspr, with drug loading. These studies indicate that DOX intercalates at its high-affinity sequence bound at the AuNP, and that ActD exhibits relatively weaker binding to its preferred sequence. Agarose gel electrophoresis further confirmed drug binding and revealed that particle mobilities inversely correlate with Dh. The equilibrium binding constant, K, and dissociation rate constant, β, were determined by dialysis. Results indicate that the high negative electrostatic potential within the DNA shell of the particle significantly decreases β and enhances K for DOX but has little effect on K and β for ActD. The cytotoxicity of the vehicles was studied, with IC50 = 5.6 ± 1.1 μM and 46.4 ± 9.3 nM for DOX-DNA-AuNP and IC50 = 0.12 ± 0.07 μM and 0.76 ± 0.46 nM for ActD-DNA-AuNP, in terms of drug and particle concentrations, respectively.

Original languageEnglish (US)
Pages (from-to)2061-2070
Number of pages10
JournalBioconjugate Chemistry
Volume23
Issue number10
DOIs
StatePublished - Oct 17 2012

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Dactinomycin
Cytotoxicity
Antineoplastic Agents
Nanoparticles
Doxorubicin
DNA
Pharmaceutical Preparations
Inhibitory Concentration 50
Nucleic Acid Denaturation
Dialysis
Surface Plasmon Resonance
Agar Gel Electrophoresis
Oligonucleotides
Drug and Narcotic Control
Surface plasmon resonance
Hydrodynamics
Intercalation
Electrophoresis
Static Electricity
Gold

ASJC Scopus subject areas

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

Cite this

Investigation of the drug binding properties and cytotoxicity of DNA-capped nanoparticles designed as delivery vehicles for the anticancer agents doxorubicin and actinomycin D. / Alexander, Colleen M.; Dabrowiak, James C.; Maye, Mathew M.

In: Bioconjugate Chemistry, Vol. 23, No. 10, 17.10.2012, p. 2061-2070.

Research output: Contribution to journalArticle

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