title: A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia.
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.
authors.affiliation: College of Pharmacy, The Ohio State University, 500 W 12th Ave, 43210, Columbus, Ohio, USA. lee.1339@osu.edu.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Songlin
authors.initials: S
authors.lastname: Xu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Yang
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.forename: Bryant C
authors.initials: BC
authors.lastname: Yung
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D008055:Lipids / Q000737:chemistry; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D034741:RNA, Small Interfering; D014168:Transferrin