Enhanced drug delivery using sonoactivatable liposomes with membrane-embedded porphyrins
a Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
b Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China
c Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
Small molecules that interfere with nucleic acid are widely used in chemotherapy, however, improved delivery approaches are required to improve anti-tumor outcomes. Here, we present the development of an ultrasoundactivatable porphyrin-phospholipid-liposome (pp-lipo) that responds to low intensity focused ultrasound (LIFU) for sonodynamic therapy (SDT). The pp-lipo is constructed by incorporating a small proportion of porphyrin (pyropheophorbide) conjugated lipid into a liposome formulation. This enables sonosensitization-induced lipid oxidation and efficient disruption of liposomes to release loaded doxorubicin (Dox). This results in increased Dox nuclear subcellular location and cytotoxicity in cancer cells in vitro upon pp-lipo exposure to LIFU. Following intravenous administration, LIFU enhanced deposition of Dox within tumor tissue, suppressed tumor growth, and also increased porphyrin near infrared tumor fluorescence. Thus, pp-lipo is a versatile carrier that can be extended to many ultrasound-controllable drug delivery applications.