Effects of Surface Charge, PEGylation and Functionalization with Dipalmitoylphosphatidyldiglycerol on Liposome–Cell Interactions and Local Drug Delivery to Solid Tumors via Thermosensitive Liposomes
M. Petrini, Wouter J.M. Lokerse, Agnieszka Mach, Martin Hossann, Olivia M. Merkel, Lars H. Lindner
Abstract
PURPOSE: - and PEG-functionalized liposomes, focusing on the delivery of a well-known cytotoxic drug (doxorubicin; DOX) in combination with local hyperthermia (HT, 41-43°C). MATERIALS AND METHODS: -CTSL/PEG-CTSL) were thoroughly analyzed for size, surface charge, and heat-triggered DOX release. Cancer cell targeting and DOX delivery was evaluated by FACS, fluorescence imaging, and HPLC. In vivo particle behavior was analyzed by assessing DOX biodistribution with local HT application in tumor-bearing animals. RESULTS: -CTSL promoted more efficient liposome-cell interactions, resulting in a higher DOX delivery and cancer cell toxicity compared with PEG-CTSL. By exploiting the dual-targeting function of CTSLs, we were able to selectively trigger DOX release in the intracellular compartment by HT. When tested in vivo, local HT promoted an increase in intratumoral DOX levels for all (C)TSLs tested, with DOX enrichment factors ranging from 3 to 14-fold depending on the type of formulation. CONCLUSION: lipid in designing liposomes for tumor-targeted applications.