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Her2 Antibody-mediated Drug Delivery And Targeted Therapy

Posted on:2017-07-24Degree:MasterType:Thesis
Country:ChinaCandidate:H X DiFull Text:PDF
GTID:2334330485982761Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Over the years, cancer has been a big threat to human health. Chemotherapy is the most common method for treating cancer currently, however, it still has big drawbacks such as side-effect caused by its non-specificity. Photodynamic therapy (PDT) is a new method of treating cancer rising in recent years. Wherein the photosensitizer is a key substance. However, most photosensitizers are insoluble in water, or polymerize readily under physiological conditions, which greatly limits the development of PDT. In this experiment, we prepared Her2 targeting photosensitive liposomes by film coating method, hydrophobic indocyanine green was loaded onto the membrane of the liposomes, and Adriamycin (doxorubicin, DOX) was loaded in the water phase by the ammonium sulfate gradient method.In this study, we selected the opimized prescription by single factor experiments. The diameter of the photosensitive liposomes (PSL) we prepared was 128.1±1.8nm, and it had a uniform particle size and high stability. PSL also showed clear structure and good morphology. DOX encapsulation efficiency was up to 90%. The result of the determinations of factors which influenced entrapment efficiency showed the determination method we used was scientific, and the data we obtained was accurate and reliable. The results of in vitro release studies showed that DOX released from the light-sensitive liposomes rapidly and continuously upon the near-infrared light (NIR) laser irradiation. The cumulative release of DOX increased by nearly 20% than the absence of NIR irradiation in 6h. It can be seen that NIR laser triggered the release of DOX from the liposome obviously.On the basis of the above light-sensitive liposomes, we further prepared Her2 targeted photosensitive liposomes (Her2-PSL). In MCF-7 and A549 cellular uptake experiments, the amount of Her2-PSL in MCF-7 cells was far more than A549 cells. It was demonstrated that the targeted liposomes may be specifically uptake by positive Her2 receptor expressed MCF-7 cells. The in vivo distribution experiment of MCF-7 or A549 tumors bearing in mice showed that fluorescence signal of MCF-7 tumor was significantly stronger than that of A549 tumors, suggesting that targeted photosensitive liposomes could be specifically delivered to MCF-7 tumor. In the anti-tumor pharmacodynamics study, Her2-PSL could be targeted to the MCF-7 tumor tissue selectively, and lots of DOX released from the liposomes after the NIR irradiation, achieving a synergistic therapy of chemotherapy and PDT. The experimental results showed that the tumor inhibition rate of the treatment group was 93.6% after NIR irradiation, and the weight curve fluctuate was little, showing the safety of anti-tumor effect. The co-therapy had such a significant effect that we believe it will have a bright prospect.
Keywords/Search Tags:Photosensitive liposomes, ICG, Her2 anti-body, Active-targeting therapy, Co-therapy
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