Abstract

Localised drug delivery to tumours may be applied using blood compatible nano sized carriers able to respond to an external stimulus with a triggered drug release. Conventional thermos-sensitive liposomes (TSLs) or similar delivery systems lack the labels for in vivo tracking or clinical imaging and hence the ability to assess the optimal trigger time post administration. We develop labelled thermosensitive liposomal (iTSL) delivery system for localised delivery by Focussed Ultrasound (FUS) triggered release. In addition to labelling for MRI , we introduced a near-infrared fluorescence (NIRF) label which greatly assists real time tracking of the carrier in our murine xenograft cancer model. This in turn allows for optimisation of the FUS conditions and timings, required for triggered-release and functional delivery of the therapeutic drugs to tumours. We synthesise these as lipid attached conjugates to ensure specific and lasting labelling of the carrier liposomes. MRI contrast enhancement ability and NIRF signals are assessed in vitro and in vivo. Nanoparticle (iTSLs) kinetics in murine tumours are assessed with optical imaging and at defined time intervals post intravenous injection, FUS was applied to induce a small increase in temperature to 42-43°C for 3-5 minutes. Imaging reveals both dramatic nanoparticles accumulation and drug release immediately after FUS treatment. Significant tumour growth inhibition is observed for the FUS treated tumours compared to those that were treated only with the drug nanoparticles. The applications of such multifunctional nanotheranostics with short and repeated FUS applications could have a transformative effect on cancer chemotherapy.