HDL-AuNPs-BMS Nanoparticle Conjugates as Molecularly Targeted Therapy for Leukemia

Na Shen, Fei Yan, Jiuxia Pang, Zhe Gao, Aref Al-Kali, Christy L. Haynes, Mark R. Litzow, Shujun Liu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Gold nanoparticles (AuNPs) with adsorbed high-density lipoprotein (HDL) have been utilized to deliver oligonucleotides, yet HDL-AuNPs functionalized with small-molecule inhibitors have not been systematically explored. Here, we report an AuNP-based therapeutic system (HDL-AuNPs-BMS) for acute myeloid leukemia (AML) by delivering BMS309403 (BMS), a small molecule that selectively inhibits AML-promoting factor fatty acid-binding protein 4. To synthesize HDL-AuNPs-BMS, we use AuNP as a template to control conjugate size ensuring a spherical shape to engineer HDL-like nanoparticles containing BMS. The zeta potential and size of the HDL-AuNPs obtained from transmission electron microscopy demonstrate that the HDL-AuNPs-BMS are electrostatically stable and 25 nm in diameter. Functionally, compared to free drug, HDL-AuNPs-BMS conjugates are more readily internalized by AML cells and have more pronounced effects on downregulation of DNA methyltransferase 1 (DNMT1), induction of DNA hypomethylation, and restoration of epigenetically silenced tumor suppressor p15INK4B coupled with AML growth arrest. Importantly, systemic administration of HDL-AuNPs-BMS conjugates into AML-bearing mice inhibits DNMT1-dependent DNA methylation, induces AML cell differentiation, and diminishes AML disease progression without obvious side effects. In summary, these data, for the first time, demonstrate HDL-AuNPs as an effective delivery platform with great potential to attach distinct inhibitors and HDL-AuNPs-BMS conjugates as a promising therapeutic platform to treat leukemia.

Original languageEnglish (US)
Pages (from-to)14454-14462
Number of pages9
JournalACS Applied Materials and Interfaces
Volume10
Issue number17
DOIs
StatePublished - May 2 2018

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint Dive into the research topics of 'HDL-AuNPs-BMS Nanoparticle Conjugates as Molecularly Targeted Therapy for Leukemia'. Together they form a unique fingerprint.

  • Cite this