A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

Zhaogang Yang, Bo Yu, Jing Zhu, Xiaomeng Huang, Jing Xie, Songlin Xu, Xiaojuan Yang, Xinmei Wang, Bryant C. Yung, L. James Lee, Robert J. Lee, Lesheng Teng

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Abstract

The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.

Original languageEnglish (US)
Pages (from-to)9742-9751
Number of pages10
JournalNanoscale
Volume6
Issue number16
DOIs
StatePublished - Aug 21 2014

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ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Yang, Z., Yu, B., Zhu, J., Huang, X., Xie, J., Xu, S., Yang, X., Wang, X., Yung, B. C., Lee, L. J., Lee, R. J., & Teng, L. (2014). A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia. Nanoscale, 6(16), 9742-9751. https://doi.org/10.1039/c4nr01510j