The Preparation Of Photocontrolled-release Liposome And Its Combined Antitumor Therapeutic Effect

Malignant tumor seriously threats human’s life and health.Many antitumor drugs,such as chemotherapy and radiotherapy drugs,have negative influence on the treatment of patients due to their lack of tumor targeting and serious side effects.Multidrug combination therapy based on tumor targeting drug delivery systems（DDSs）exhibits great potential for cancer treatment.Among them,the stimulus-sensitive drug delivery systems can further improve the tumor targeting and enhance the therapeutic effect by controlling drug release at tumor sites.In this study,phospholipid materials DPPC（1,2-dipalmitoyl-sn-glycero-3-phosphocholine）and photosensitizers Zn Pc（PEG）₄（2-（12-hydroxy-1,4,7,10-tetraoxadodecyl）phthalocyaninatozinc）were used to construct thermosensitive liposomes for molecular imaging,photodynamic and photothermal therapy,together with doxorubicin（DOX）for chemotherapy.The results showed that Zn Pc（PEG）₄could reduce the particle size of DPPC liposomes and improve the stability of packaged DOX.Compared with the Zn Pc（PEG）₄@Li POs with only photosensitizer loaded and DOX@Li POs with only doxorubicin loaded,Zn Pc（PEG）₄:DOX@Li POs had enhanced ROS production capacity,heat generation property,and photo-triggered doxorubicin release effect.The results of cell experiments showed that Zn Pc（PEG）₄:DOX@Li POs had higher cytotoxicity and caused more apoptotic cell proportion,which proved the synergistic tumor cell killing effect of Zn Pc（PEG）₄and DOX.Liposomes loaded with Zn Pc（PEG）₄produced more intracellular ROS than free Zn Pc（PEG）₄at the same concentration.Furthermore,cell localization experiments showed that Zn Pc（PEG）₄:DOX@Li POs was distributed in both lysosomes and mitochondria,suggesting the mechanism of its activity.In vivo studies on tumor-bearing mice showed that Zn Pc（PEG）₄:DOX@Li POs had enhanced tumor accumulation,increased antitumor effect and reduced liver retention.Histopathological analysis showed that there was no significant damage to the vital organs.The liposomes constructed by photosensitizer Zn Pc（PEG）₄are targeted controlled release drug delivery systems combined with phototherapy function,which can be applied for targeted delivery of other antitumor drugs,and have excellent application value.