Study On The Antitumor Effect Of Temperature Sensitive Quercetin Liposome Guided By Aptamer

Nowadays,malignant tumor has ranked the first killer of the whole human beings.So,how to treat malignant tumors effectively has been an urgent problem to solve.In order to reduce the pain and improve the accuracy of the anti-cancer drugs treatment,encapsulation of anti-cancer drugs into targeted delivery carrier is one of the the most effective solutions.As aptamer AS1411 is a nucleocapsid specific aptamer which can bind to the nucleocapsid that overexpressed on the surface of tumor cell membrane,it can increase the tumor targeting of the anticancer drug delivery carrier greatly if the system linked with AS1411.On the other hand,we use temperature sensitive liposomes for the encapsulation of quercetin for the encapsulated drugs temperature stimulation-response release.In this study,temperature responsive and aptamer modified drug loaded liposomes(AQTSL)were constructed for the targeting carrying and centralized releasing of quercetin,and the antitumor effect of the drug loading system in vitro and in vivo was further studied.Firstly,the optimal preparation technology of QTSL was obtained by orthogonal experiment and the drug encapsulation rate reached 69.8±0.71% under ideal preparation conditions.The liposomes were spherical and well dispersed with the particle size of120.9 ± 0.71 nm and the zeta potential of-7.1 ± 0.62 mV by TEM observation and Zetasizer measurement.QTSL was incubated under the different temperatures from 37?to 43? respectively,and the results showed that QTSL could achieve rapid drug release within 7 minutes at 42?.Secondly,we prepared AQTSL by coupling experiment to link AS1411 on QTSL further.Agarose gel electrophoresis,UV spectroscopy,particle size,potential results and mass spectrum experimental results all showed that aptamer AS1411 has been modified onto QTSL successfully.MTT assay was used to study the anti-tumor effect of AQTSL on HeLa cells at different temperature and different concentration in vitro.Cell proliferation experiment showed that QTSL and AQTSL inhibited theproliferation of HeLa and SW480 cells significantly.The results of MTT and flow cytometry showed that AQTSL could target HeLa cells in vitro either.The results of animal experiment showed that AQTSL had significant antitumor effect on U14 cells,and the inhibition rate reached 75% with no significant side effect on mice.To sum up,this study showed that AQTSL exhibited tumor-targeting and specific temperature releasing characteristic and could achieve precise treatment to tumor in cooperation with chemotherapy.This study will provide new ideas for the treatment of cancer.