Combinatorial drug conjugation enables nanoparticle dual-drug delivery

Santosh Aryal, Che Ming Jack Hu, Liangfang Zhang

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


A new approach to loading multiple drugs onto the same drug-delivery nanocarrier in a precisely controllable manner, by covalently preconjugating multiple therapeutic agents through hydrolyzable linkers to form drug conjugates, is reported. In contrast to loading individual types of drugs separately, this drug-conjugates strategy enables the loading of multiple drugs onto the same carrier with a predefined stoichiometric ratio. The cleavable linkers allow the therapeutic activity of the individual drugs to be resumed after the drug conjugates are delivered into the target cells and unloaded from the delivery vehicle. As a proof of concept, the synthesis and characterization of paclitaxel-gemcitabine conjugates are demonstrated. The time-dependent hydrolysis kinetics and cytotoxicity of the combinatorial drug conjugates against human pancreatic cancer cells are examined. It is shown that the synthesized drug conjugates can be readily encapsulated into a lipid-coated polymeric drug-delivery nanoparticle, which significantly improves the cytotoxicity of the drug conjugates as compared to the free drug conjugates.

Original languageEnglish (US)
Pages (from-to)1442-1448
Number of pages7
Issue number13
StatePublished - Jul 5 2010


  • Cancer therapy
  • Conjugation
  • Drug delivery
  • Lipid-polymer hybrids
  • Nanoparticles

ASJC Scopus subject areas

  • Biomaterials
  • Engineering (miscellaneous)
  • Biotechnology
  • Medicine(all)


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