Strategy for increasing drug solubility and efficacy through covalent attachment to polyvalent DNA-nanoparticle conjugates

Xue Qing Zhang, Xiaoyang Xu, Robert Lam, David Giljohann, Dean Ho, Chad A. Mirkin

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Paclitaxel, a potent chemotherapeutic utilized in a variety of cancers, can be limited in its effectiveness due to inherent insolubility in aqueous media and acquired chemoresistance within certain cells. An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50-fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. Internalized conjugates demonstrate increased activity as compared with free drug across a variety of cell types, including a Paclitaxel-resistant cell line. Attachment to DNA-nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media.

Original languageEnglish (US)
Pages (from-to)6962-6970
Number of pages9
JournalACS Nano
Volume5
Issue number9
DOIs
StatePublished - Sep 27 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Keywords

  • DNA
  • Paclitaxel
  • cancer
  • chemoresistance
  • gold
  • nanomedicine
  • nanoparticle

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