Photo-triggered release of doxorubicin from liposomes formulated by amphiphilic phthalocyanines for combination therapy to enhance antitumor efficacy

Abstract

Multidrug combination therapy based on drug delivery systems (DDSs) has great potential for cancer treatment. Stimuli-sensitive DDSs further enhance therapeutic efficacy by providing controllable drug delivery. Herein, the phospholipid compound DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) was used to construct thermosensitive liposomes to load the photosensitizer ZnPc(PEG)₄ (zinc phthalocyanine substituted by tetraethylene glycol) for molecular imaging, and photodynamic and photothermal therapy, together with doxorubicin (DOX) for chemotherapy. Interestingly, ZnPc(PEG)₄ as an amphipathic molecule was found to be important in the construction of the liposomes, and it provided liposomes with improved stability. The thus-obtained liposomes ZnPc(PEG)₄:DOX@LiPOs were demonstrated to have enhanced ROS production capacity, heat generation properties and a photo-triggered doxorubicin release effect, and, in cellular experiments, increased cytotoxicity and apoptotic cell proportions, compared to ZnPc(PEG)₄@LiPOs and DOX@LiPOs. ZnPc(PEG)₄ loaded in lipid bilayers showed stronger intracellular ROS production ability compared to free ZnPc(PEG)₄. In vivo studies indicated that ZnPc(PEG)₄:DOX@LiPOs exhibited enhanced tumor accumulation, increased anti-cancer effects and reduced liver retention. These photo-triggered liposomes constructed by the photosensitizer ZnPc(PEG)₄ can also be used to package other cargo for combined target tumor therapy and molecular imaging.