Characterization of high-affinity peptides and their feasibility for use in nanotherapeutics targeting leukemia stem cells

Hongyong Zhang, Juntao Luo, Yuanpei Li, Paul Henderson, Yanchun Wang, Sebastian Wachsmann-Hogiu, Weixin Zhao, Kit Lam, Chong-Xian Pan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Peptides featuring the LR(S/T) motif were identified that could specifically bind to the C-type lectin-like molecule-1 (CLL1), a protein preferentially expressed on acute myeloid leukemia stem cells (LSCs). Micellar nanoparticles were covalently decorated with CLL1-targeting peptides for targeted drug delivery. The resulting peptide-coated nanoparticles were 13.5 nm in diameter and could be loaded with 5 mg of daunorubicin per 20 mg of telodendrimers. These "targeting nanomicelles" transported the drug load to the interior of cells expressing CLL1 and to LSCs isolated from clinical specimens in vitro, but did not bind to normal blood or normal hematopoietic stem cells. The presence of CLL1-targeting peptides on the surface of the nanomicelles enabled the improved binding and delivery of substantially more daunorubicin into the cells expressing CLL1 and CD34+ leukemic cells compared with unmodified nanomicelles. In conclusion, nanomicelles coated with CLL1-targeting peptides are potentially useful for eradicating LSCs and improving leukemia therapy. From the Clinical Editor: Micellar nanoparticles covalently decorated with targeting peptides were used for targeted drug delivery of daunorubicin to address acute myeloid leukemia stem cells.

Original languageEnglish (US)
Pages (from-to)1116-1124
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume8
Issue number7
DOIs
StatePublished - Oct 2012

    Fingerprint

Keywords

  • Acute myeloid leukemia
  • C-type lectin-like molecule-1
  • Leukemia stem cells
  • Nanoparticles
  • Targeted therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Medicine (miscellaneous)
  • Pharmaceutical Science

Cite this