Preparation Of Doxorubicin Magnetic Targeting-photosensitive Liposomes And Its Application In Combined Photothermal-Chemotherapy Of Cancer

Liposomes,as a commonly used drug carrier,can effectively enhance the stability of the drug and reduce its side effects.However,conventional liposomes are often failed to achieve the controlled release in the pathologic site.Photothermal therapy?PTT?is a emerging technique,which presents a promising application for cancer therapy.Fe₃O₄ magnetic nanoparticles with low toxicity,superparamagnetism and excellent photothermal conversion properties,can be used as an ideal photosensitizer for PTT.In this paper,we have constructed a multifunctional drug carrier with both magnetic targeting,photothermal and thermosensitive release properties based on the Fe₃O₄ nanoparticles and thermosensitive liposomes?TSL?,called magnetic targeting-photosensitive liposomes?Fe₃O₄-TSL?.Doxorubicin?DOX?was used as a model drug,and it was loaded into the carrier via ammonium sulfate gradient method to construct doxorubicin magnetic targeting-photosensitive liposomes?DOX&Fe₃O₄-TSL?which was then applied to the study on in vitro and in vivo combined photothermal-chemotherapy of cancer.Concrete study content as follows:1.The oil-soluble Fe₃O₄ magnetic nanoparticles and Fe₃O₄-TSL drug carrier were prepared by high temperature thermal decomposition and reverse evaporation method,respectively,and their properties were characterized.It was found that the as-synthesized Fe₃O₄ nanoparticles had near-infrared absorption property and exhibited superparamagnetism and magnetism.The nanoparticles were encapsulated in the lipid bilayer which caused a particle size increase of the liposomes,but not affectted its phase transition temperature.In addition,the Fe₃O₄-TSL showed excellent in vitro magnetic resonance response and near-infrared?NIR?photothermal effect.The MCF-7 cancer cell was selected as the model to investigate the cytotoxicity,the result indicated that Fe₃O₄-TSL had a low toxicity and good biocompatibility.2.The DOX loading of TSL and Fe₃O₄-TSL was carried out by ammonium sulfate gradient method.By comparing with the NIR controlled release effect of DOX&Fe₃O₄-TSL and DOX-TSL,it could be seen that the encapsulation of Fe₃O₄ nanoparticles in the liposomes made DOX to be released by NIR trigger.The results of cell experiments showed that DOX&Fe₃O₄-TSL could be uptaken by tumor cells,and DOX could be released and then entered into the nucleus after irradiated with NIR laser.The in vitro anti-tumor study of DOX&Fe₃O₄-TSL proved that chemo-photothermal therapy was obviously superior to PTT alone.3.The in vivo tumor targeting and anti-tumor effect of DOX&Fe₃O₄-TSL were studied with S180 tumor-bearing mice.After intravenous injection,Fe₃O₄-TSL tended to enrich in the tumor over time and showed remarkable in vivo MRI and photothermal effects.The result of in vivo anti-tumor experiment demonstrated that chemo-photothermal therapy of DOX&Fe₃O₄-TSL was obviously superior to PTT or chemotherapy alone.In addition,the histopathological examination indicated that no significant damage was caused by DOX&Fe₃O₄-TSL to the normal tissues during the course of therapy.