(566c) Magnetic Nanoparticle-Triggered Liposomal Drug Delivery for Cancer Imaging and Treatment

We will describe drug release from liposomes formulated with superparamagnetic iron oxide nanoparticles (SPION) and drugs for potential applications in magnetic resonance imaging (MRI) and hyperthermia-mediated drug release. SPION are a class of MRI contrast agents and depending on the crystal size of the iron oxide they can also be used as hyperthermia agents via excitation by an alternative magnetic field (AMF). Liposomes can encapsulate drugs in either the bilayer or inner aqueous phase. Therefore, combination of liposomes and SPION can be used to meet the requirements for cancer treatment. In this study, we use calcein and doxorubicin (DOX) as the model drug agents. Doxorubicin loading protocols using the pH gradient strategy and methods for SPION incorporation in aqueous phase of liposomes (magnetoliposomes) have been reported in literature. However, attempts to co-encapsulate doxorubicin and SPION in the liposomes have been limited due to interactions of negative charged SPION with the positively charged DOX resulting in aggregation. Our studies show that the encapsulation of DOX and SPION results in complexation of the two agents followed by precipitation in solution. In addition, the current pH gradient method for maximizing doxorubicin encapsulation causes release of iron from SPION. We have investigated new strategies to prevent the precipitation of the two agents and maximize drug encapsulation, by modifying SPION surface electrostatically and hydrophobically. We screened out several SPION for hyperthermia agent using thermo-sensitive liposome formulation and tested nanoparticle-triggered liposomal drug delivery in a gel system. We will also discuss our approaches for nanoparticle-triggered liposomal drug delivery and how the surface properties of SPION affect the encapsulation of SPION and drugs.