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
A B S T R A C T
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.