Synthesis and evaluation of clickable block copolymers for targeted nanoparticle drug delivery

Siyan Zhang, Kiat Hwa Chan, Robert K. Prud'Homme, A. James Link

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Polymeric nanoparticles with multifunctional capabilities, including surface functionalization, hold great promise to address challenges in targeted drug delivery. Here, we describe a concise, robust synthesis of a heterofunctional polyethylene glycol (PEG), HO-PEG-azide. This macromer was used to synthesize polylactide (PLA)-PEG-azide, a functional diblock copolymer. Rapid precipitation of this copolymer with a hydrophobic cargo resulted in the generation of monodisperse nanoparticles with azides in the surface corona. To demonstrate conjugation to these nanoparticles, a regioselectively modified alkyne-folate was employed as a model small molecule ligand, and the artificial protein A1 with an alkyne moiety introduced by unnatural amino acid substitution was selected as a model macromolecular ligand. Using the copper-catalyzed azide-alkyne ligation reaction, both ligands exhibited good conjugation efficiency even when low concentrations of ligands were used.

Original languageEnglish (US)
Pages (from-to)2228-2236
Number of pages9
JournalMolecular Pharmaceutics
Issue number8
StatePublished - Aug 6 2012

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science


  • bioconjugation
  • bioorthogonal reactions
  • click chemistry
  • nanoparticles


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