Unique Contributions of iDQC MR Contrast to Stimuli-Sensitive Liposomal Chemotherapy and Imaging

Abstract

<p>Liposomes are excellent chemotherapy drug delivery agents, on the cutting edge of cancer treatment technology. Since liposomes are already used to deploy cancer drugs in patients, imaging capacity would make them dual-purpose "theranostic" vesicles. Intermolecular double quantum coherence (iDQC) MRI is uniquely suited to this application, as its contrast does not require any additional chemicals. Adding contrast agents to liposomes can be time-consuming, add to toxicity, interfere with membrane function, or adversely affect drug loading. Furthermore, iDQC contrast measures diffusion and thus directly depends on membrane permeability and related properties. In this set of experiments, it has been shown that iDQC signal from intra-liposomal water can be distinguished from that of bulk water, and that the T2 dynamics of intra-liposomal water are predictable and dependent on the percent of water encapsulated. These techniques to distinguish between water molecules based on their current physical circumstances lead to many novel possibilities in MRI, as nearly all the signal in conventional MRI is from water protons. Based on the signal to noise ratio in the aforementioned iDQC experiments, we predict that iDQC contrast from liposomes will be visible in vivo, and propose to prove this in a murine model. By examining intra-liposomal water, iDQC can be used to improve chemotherapy delivery via real time monitoring of liposome location and drug release.</p>