CD33-Targeted lipid nanoparticles (aCD33LNs) for therapeutic delivery of GTI-2040 to acute myelogenous leukemia

Hong Li, Songlin Xu, Jishan Quan, Bryant C. Yung, Jiuxia Pang, Chenguang Zhou, Young Ah Cho, Mengzi Zhang, Shujun Liu, Natarajan Muthusamy, Kenneth K. Chan, John C. Byrd, L. James Lee, Guido Marcucci, Robert J. Lee

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


CD33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added as a targeting ligand. The delivery efficiency of this system was investigated both in vitro and in vivo. When cells were treated with aCD33LN/GTI-2040, significant uptake was observed in CD33 positive Kasumi-1 cells. aCD33LNs loaded with GTI-2040 induced significant down-regulation of R2 mRNA and protein levels in AML cells. Moreover, aCD33LN/GTI-2040 showed a 15-fold reduction in the IC50 of antileukemic drug Ara-C in Kasumi-1 cells. In Kasumi-1 xenograft model, aCD33LN/GTI-2040 showed significant R2 downregulation compared to LN/GTI-2040. Furthermore, aCD33LN/GTI-2040 coadministered with Ara-C was shown to be highly effective in tumor growth inhibition and to greatly increase survival time of mice bearing Kasumi-1 xenograft tumors. The conjugate DOC-PEI has shown an ability to include calcein release from lipid nanoparticles, suggesting a potential mechanism contributing to efficient endosome release by DOC-PEI2K. These results indicate that aCD33LNs are a highly effective vehicle for the therapeutic delivery of antisense agents to AML.

Original languageEnglish (US)
Pages (from-to)2010-2018
Number of pages9
JournalMolecular pharmaceutics
Issue number6
StatePublished - Jun 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.


  • CD33-targeting
  • GTI-2040
  • acute myelogenous leukemia
  • antisense oligonucleotide
  • deoxycholate-polyethylenimine conjugate
  • lipid nanoparticles


Dive into the research topics of 'CD33-Targeted lipid nanoparticles (aCD33LNs) for therapeutic delivery of GTI-2040 to acute myelogenous leukemia'. Together they form a unique fingerprint.

Cite this