MRI-Guided Thermosensitive Liposomal Drug Delivery for Cancer Therapy
Po-Wah So1, Maral Amrahli2, Michael Wright2, Miguel Centelles2, Wladyslaw Gedroyc3, Andrew Miller2, and Maya Thanou2

1Neuroimaging, King's College London, London, United Kingdom, 2Institute of Pharmaceutical Sciences, King's College London, London, United Kingdom, 3Experimental Medicine, Imperial College London, london, United Kingdom


We have designed and synthesised a novel liposome formulation, capable of releasing encapsulated drug on targeting/heating by focussed ultrasound (FUS) for cancer therapy and being visualised by MRI due to the incorporation of gadolinium chelates. We show the novel liposomes are targeted to tumours by FUS and MRI-visible in vivo and thus, suitable for theranostic applications in cancer.


Novel theranostic liposomal-based nanoparticles for cancer treatment.


'Theranostic' nanotechnology aims to use the same drug and delivery system to achieve diagnostic imaging and therapy simultaneously1. We will develop novel gadolinium-chelate labelled, drug-loaded liposomal nanoparticles that are MRI-visible, as well as capable of delivering and releasing drugs when activated by a localising technique such as focused ultrasound (FUS, Fig. 1). We have shown how incorporation of gadolinium chelate-conjugated lipids in liposomes has enabled these nanoparticles to be MRI-visible2. In this study, we will design and synthesise a novel liposome formulation, rendered MRI-visible by incorporation of gadolinium-chelate conjugated lipids that can encapsulate and deliver drugs to be released on heat exposure by FUS.


Chelating ligands were conjugated to the lipid, N,N-distearylamidomethylamine prior to chelation of Gd3+. Image-guided thermosensitive PEGylated liposomal (ITLs) nanoparticles were prepared and loaded with doxorubicin. For near-infrared fluorescence (NIRF) imaging, lipids conjugated to a near-infrared fluorophore were also incorporated into the ITLs.

ITLs were characterised in vitro by T1-MRI relaxometry at 7T and NIRF imaging with FUS-induced drug release determined by fluorescence imaging. ITLs were visualised in vivo by MRI and NIRF imaging following intravenous injection into mice bearing human xenograft tumours on both flanks, with one flank being exposed to short-term heating by FUS.

Results and Discussions

In vitro: The novel ITLs were visible by NIRF imaging (Fig. 2a). Doxorubicin itself is also fluorescent (Fig. 2b) and its fluorescence increased when released from liposomes by FUS (Fig. 2c). T1-weighted MRI shows positive enhancement of the liposomal formulation compared to water (Fig. 2d and e).

In vivo: NIRF imaging confirms the accumulation of ITLs in the xenograft tumours following administration but significantly higher in the tumours exposed to FUS (Fig. 3). This is consistent with the greater signal enhancement by T1-weighted MRI of the FUS-exposed tumour (Fig. 4). Note, FUS was not purely localised to the tumour and underlying tissue structures including the hind legs were also exposed and signal enhancement is also observed.


We have shown our novel ITLs are indeed visible by MRI and that they can be targeted by FUS to deliver and release a cytotoxic drug, paving the way for their theranostic applications in cancer therapy.


Thanks to the Republic of Azerbaijan Ministry of Education, Engineering and Physical Sciences Research Council UK, King's Commercialisation Institute for funding MA and this work. Also to the British Heart Foundation for funding the 7T MRI scanner.


1Thanou, M. and Gedroyc, W. (2013). MRI-Guided Focused Ultrasound as a New Method of Drug Delivery. Drug Delivery. 2013: 616197.

2Kamaly, N., Kalber, T., Ahmad, A., Oliver, M. H., So, P-W., Herlihy, A. H., Bell, J. D., Jorgensen, M. R. & Miller, A. D. (2008). Bimodal paramagnetic and fluorescent liposomes for cellular and tumor magnetic resonance imaging. Bioconjugate Chemistry. 19: 118-129.


Theranostic technology: Thermally-sensitive liposomes are visualised in target tissue and encapsulated drug released by focussed ultrasound at target area.

(a) Near-infrared fluorescence image of the novel image-guided thermosensitive liposomes (ITLs); fluorescence imaging of the ITLs before (b) and after heating and release of doxorubicin by focussed ultrasound (FUS, note - drug fluorescence signal is quenched when liposome encapsulated) and (d) and (e) are T1-weighted MR images of water and ITLs, respectively.

In vivo near-infrared fluorescence image of a mouse with human xenografts on both flanks without and with application of focussed ultrasound (a and b, respecitively) at 3h after a tail vein injection of the novel liposomal formulation.

In vivo T1-weighted MRI of a mouse with human xenografts on both flanks without and with application of focussed ultrasound (a and b, respecitively) at 4-5h after a tail vein injection of the novel liposomal formulation.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)