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 Citations (Scopus)

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

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Lipoproteins
HDL Lipoproteins
Nanoparticles
DNA
Methyltransferases
2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid
Bearings (structural)
Fatty Acid-Binding Proteins
Molecules
Oligonucleotides
Zeta potential
Fatty acids
Gold
Restoration
Tumors

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Shen, N., Yan, F., Pang, J., Gao, Z., Al-Kali, A., Haynes, C. L., ... Liu, S. (2018). HDL-AuNPs-BMS Nanoparticle Conjugates as Molecularly Targeted Therapy for Leukemia. ACS Applied Materials and Interfaces, 10(17), 14454-14462. https://doi.org/10.1021/acsami.8b01696

HDL-AuNPs-BMS Nanoparticle Conjugates as Molecularly Targeted Therapy for Leukemia. / Shen, Na; Yan, Fei; Pang, Jiuxia; Gao, Zhe; Al-Kali, Aref; Haynes, Christy L.; Litzow, Mark R; Liu, Shujun.

In: ACS Applied Materials and Interfaces, Vol. 10, No. 17, 02.05.2018, p. 14454-14462.

Research output: Contribution to journalArticle

Shen, N, Yan, F, Pang, J, Gao, Z, Al-Kali, A, Haynes, CL, Litzow, MR & Liu, S 2018, 'HDL-AuNPs-BMS Nanoparticle Conjugates as Molecularly Targeted Therapy for Leukemia', ACS Applied Materials and Interfaces, vol. 10, no. 17, pp. 14454-14462. https://doi.org/10.1021/acsami.8b01696
Shen, Na ; Yan, Fei ; Pang, Jiuxia ; Gao, Zhe ; Al-Kali, Aref ; Haynes, Christy L. ; Litzow, Mark R ; Liu, Shujun. / HDL-AuNPs-BMS Nanoparticle Conjugates as Molecularly Targeted Therapy for Leukemia. In: ACS Applied Materials and Interfaces. 2018 ; Vol. 10, No. 17. pp. 14454-14462.
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