title: Homoharringtonine delivered by high proportion PEG of long- circulating liposomes inhibits RPMI8226 multiple myeloma cells in vitro and in vivo.
abstract: Multiple myeloma (MM) remains an incurable disease in most patients. Homoharringtonine (HHT) is a natural alkaloid produced by various Cephalotaxus species, and is approved by the United States of America Food and Drug Administration to treat patients with acute and chronic myeloid lymphoma. The aim of this study was to develop the high proportion polyethyleneglycol (PEG) of long-circulating HHT liposomes (LCL-HHT-H-PEG) and investigate its therapeutic applicability in vitro and in vivo against RPMI8226 MM. The optimized formulation of LCL-HHT-H-PEG showed a higher association with cytotoxicity against MM RPMI8226 cells than those of low proportion PEG of long-circulating HHT liposomes, liposome-encapsulated-HHT, micelle-HHT, and HHT in vitro. Therapeutic experiments in severe combined immunodeficient mice implanted with MM RPMI8226 cells by the subcutaeous route showed the significant inhibition of tumor growth in LCL-HHT-H-PEG group compared with the HHT group, and other control groups. The analysis of flow cytometry and transmission electron microscopy indicated that LCL-HHT-H-PEG exerted the cytotoxicity against MM by inducing the MM apoptosis in vitro and in vivo. This study suggests that our developed LCL-HHT-H-PEG may be regarded as a promising nano-device to deliver anti-MM drug HHT for treatment of MM patients.
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Biological Science and Medical Engineering, Southeast University Nanjing 210096, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast UniversityNanjing 210009, China; Department of Gynecology and Obstetrics, Zhongda Hospital, School of Medicine, Southeast UniversityNanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast UniversityNanjing 210009, China; Department of Gynecology and Obstetrics, Zhongda Hospital, School of Medicine, Southeast UniversityNanjing 210009, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: School of Biological Science and Medical Engineering, Southeast University Nanjing 210096, China.
authors.forename: Shouhua
authors.initials: S
authors.lastname: Luo
authors.affiliation: School of Biological Science and Medical Engineering, Southeast University Nanjing 210096, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
keywords: Multiple myeloma; cytotoxicity; homoharringtonine; long-circulating liposomes; polyethyleneglycol