A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

• DOI: 10.2147/ijn.s34801
• Publication Date: 2012-09-19T00:47:49Z
• Authors: Janming Chen; Xingfa Ke; Zhiying He; Hai Gong; Yingying Zhang; Jianzhong Yao; Li Deng; Daoqiu Yang; Xiaolong Jing
• Keywords: Mesothelin

Abstract: Pancreatic cancer is a highly lethal disease with 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide novel diagnostic targeted therapy for pancreatic cancer, multifunctional nanoimmunoliposome high loading ultrasmall superparamagnetic iron oxides (USPIOs) doxorubicin (DOX) was prepared by transient binding reverse-phase evaporation method, conjugated anti-mesothelin monoclonal antibody post-insertion target anti-mesothelin-overexpressed cells. The in vitro vivo properties this antibody-conjugated PEGlyated liposomal DOX USPIOs (M-PLDU; without conjugation [PLDU]) were evaluated both human cell line Panc-1 xenograft animal model. Results showed that M-PLDUs spherical uniform diameter about ~180 nm, zeta potential −28~−30 mV, had good efficacy encapsulating USPIOs. study demonstrated possessed magnetic resonance imaging (MRI) capability transverse relaxivity (r 2 ) 58.5 mM –1 • s . Confocal microscopy more efficient uptake M-PLDU cells antibody-mediated targeting. Methyl thiazolyl tetrazolium assay results significant inhibitory effect against (half-maximal concentration, 1.95 µM). tumor signal intensity (SI) dropped significantly 4 hours after intravenous injection M-PLDU. decrease SI induced (∆ = 145.98 ± 20.45) or PLDUs 75.69 14.53) much free 42.78 22.12; P < 0.01). antitumor compared FD (free DOX) PLDU, higher on growth tissue distribution further proved could selectively accumulate xenograft. These indicated not only well retained inherent MRI USPIOs, but improved targeting therapeutic agents tissues. They may serve as promising theranostic nanomedicine detection also MRI-monitored cancer. Keywords: nanomedicine, nanoimmunoliposome, mesothelin, USPIO, doxorubicin,