title: Dynamic imaging of PEGylated indocyanine green (ICG) liposomes within the tumor microenvironment using multi-spectral optoacoustic tomography (MSOT).
abstract: Multispectral optoacoustic tomography (MSOT) is a powerful modality that allows high-resolution imaging of photo-absorbers deep within tissue, beyond the classical depth and resolution limitations of conventional optical imaging. Imaging of intrinsic tissue contrast can be complemented by extrinsically administered gold nanoparticles or fluorescent molecular probes. Instead, we investigated herein generation of re-engineered clinically-used PEGylated liposomes incorporating indocyanine green (LipoICG) as a contrast strategy that combines materials already approved for clinical use, with strong photo-absorbing signal generation available today only from some metallic nanoparticles (e.g. gold nanorods). Using MSOT we confirmed LipoICG as a highly potent optoacoustic agent and resolved tissue accumulation in tumor-bearing animals over time with high-sensitivity and resolution using two tumor models of different vascularisation. We further showcase a paradigm shift in pharmacology studies and nanoparticle investigation, by enabling detailed volumetric optical imaging in vivo through the entire tumor tissue non-invasively, elucidating never before seen spatiotemporal features of optical agent distribution. These results point to LipoICG as a particle with significant advantageous characteristics over gold nanoparticles and organic dyes.
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Beziere
authors.affiliation: Nanomedicine Lab, Faculty of Medical & Human Sciences, University of Manchester, AV Hill Building, Manchester M13 9PT, UK; UCL School of Pharmacy, Faculty of Life Sciences, University College London, Brunswick Square, London WC1N 1AX, UK.
authors.forename: Neus
authors.initials: N
authors.lastname: Lozano
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Nunes
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Juan
authors.initials: J
authors.lastname: Salichs
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Queiros
authors.affiliation: Nanomedicine Lab, Faculty of Medical & Human Sciences, University of Manchester, AV Hill Building, Manchester M13 9PT, UK; UCL School of Pharmacy, Faculty of Life Sciences, University College London, Brunswick Square, London WC1N 1AX, UK. Electronic address: kostas.kostarelos@manchester.ac.uk.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address: v.ntziachristos@tum.de.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D005453:Fluorescence; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry*; D007700:Kinetics; D008081:Liposomes; D051379:Mice; D061088:Photoacoustic Techniques / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution; D014054:Tomography / Q000379:methods*; D059016:Tumor Microenvironment
chemical_list: D003287:Contrast Media; D008081:Liposomes; D011092:Polyethylene Glycols; D007208:Indocyanine Green
keywords: Imaging; Indocyanine green; Liposome; Optoacoustic; Photoacoustic; Tumor