Preparation And In Vitro And In Vivo Activity Of A Novel Multifunctional Immunoliposome For Simultaneous Diagnosis And Therapy Of Pancreatic Cancer

With the development of molecular imaging technology,those real-time monitored and guided targeting drug delivery system based on the MRI and nano-technology have become possible.This drug delivery system can rightly improve the selectivity of anticancer drugs and MRI contrast agents to cancer cells as well as reduce adverse side effects of drugs.In this study,we constructed a novel multifunctional nano-immunoliposome loading with anticancer drug oridonin(ORI)and MRI contrast agents USPIO,with conjugated anti-mesothelin mAb to target the pancreatic cancer cells.This anti-mesothelin mAb conjugated PEGylated liposomal oridonin and USPIO(M-PLOU)was prepared by reverse-phase evaporation and post-insertion method,and we choosed the aminophosphalipid as the lipid film material and used transient bingding of oxidized dextran of USPIO with aminogroups of the aminophosphalipid to increase the trapping efficiency of USPIO.The characteristics and properties of M-PLOU were well evaluated by in vitro and vivo experiments.Results indicated that the M-PLOU has good encapsulation efficiencies of ORI and USPIO as about 89.5%and 38.5%,respectively;the targeting antibodies were successfully conjugated to the reactive maleimide terminus of the maleimide derivatized PEG2000-DSPE as well as being incorporated in the liposomal bilayers.The shape of M-PLOU was spherical and the mean particle size was about 160 nm,and the MRI measurements showed that comparing with the free USPIO,the relaxivity of M-PLOU was not changed significantly.Compared with the nontargeted PEGylated liposome(PLOU),MTT assay showed that M-PLOU had enhanced cytotoxicity toward panc-1 cells;and confocal microscopy study showed that the uptake of M-PLOU by Panc-1 cells was greater than that of PLOU without conjugated anti-mesothelin mAb.In vivo T2-weighted MRI of tumors showed that M-PLOU can significantly accumulate at the pancreatic tumor sites 4 h after intravenous injection;and in vivo anticancer activity study demonstrated that the M-PLOU had higher anticancer effectiveness than the free ORI and the PLOU.These results suggest that M-PLOU may serve as a promising nanoscale drug deliever carrier for magnetic resonance imaging(MRI)monitored targeting drug therapy of human pancreatic cancer.