Bone-targeting nanoparticle to co-deliver decitabine and arsenic trioxide for effective therapy of myelodysplastic syndrome with low systemic toxicity

Xiaoyan Wu, Zhenhua Hu, Sara Nizzero, Guodong Zhang, Maricela R. Ramirez, Ce Shi, Jin Zhou, Mauro Ferrari, Haifa Shen

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Myelodysplastic syndromes (MDS) are a diverse group of bone marrow disorders and clonal hematopoietic stem cell disorders characterized by abnormal blood cells, or reduced peripheral blood cell count. Recent clinical studies on combination therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonstrated synergy on MDS treatment, but the treatment can cause significant side effects to patients. In addition, both drugs have to be administered on a daily basis due to their short half-lives. In addressing key issues of reducing toxic side effects and improving pharmacokinetic profiles of the therapeutic agents, we have developed a new formulation by co-packaging DAC and ATO into alendronate-conjugated bone-targeting nanoparticles (BTNPs). Our pharmacokinetic studies revealed that intravenously administered BTNPs increased circulation time up to 3 days. Biodistribution analysis showed that the BTNP facilitated DAC and ATO accumulation in the bone, which is 6.7 and 7.9 times more than untargeted NP. Finally, MDS mouse model treated with BTNPs showed better restoration of complete blood count to normal level, and significantly longer median survival as compared to free drugs or untargeted NPs treatment. Our results support bone-targeted co-delivery of DAC and ATO for effective treatment of MDS.

Original languageEnglish (US)
Pages (from-to)92-101
Number of pages10
JournalJournal of Controlled Release
Volume268
DOIs
StatePublished - Dec 28 2017

Keywords

  • Arsenic trioxide
  • Bone marrow
  • Decitabine
  • Delivery
  • Myelodysplastic syndrome
  • Nanoparticle

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Bone-targeting nanoparticle to co-deliver decitabine and arsenic trioxide for effective therapy of myelodysplastic syndrome with low systemic toxicity'. Together they form a unique fingerprint.

Cite this