Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.
Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.
Tatu
T
Lajunen
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.|Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Leena-Stiina
LS
Kontturi
Department of Chemistry, Aalto University , P.O. Box 16100, FI-00076 Aalto, Finland.
Lauri
L
Viitala
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
Moutusi
M
Manna
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
Oana
O
Cramariuc
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.|Department of Physics, University of Helsinki , P.O. Box 64, FI-00014 Helsinki, Finland.
Tomasz
T
Róg
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.
Alex
A
Bunker
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.|Department of Chemistry and Bioengineering, Tampere University of Technology , P.O. Box 541, FI-33101 Tampere, Finland.
Timo
T
Laaksonen
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.
Tapani
T
Viitala
Department of Chemistry, Aalto University , P.O. Box 16100, FI-00076 Aalto, Finland.
Lasse
L
Murtomäki
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.|School of Pharmacy, University of Eastern Finland , P.O. Box 1627, FI-70211 Kuopio, Finland.
Arto
A
Urtti
D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000187:drug effects*; D005453:Fluorescence; D006046:Gold / Q000008:administration & dosage; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry*; D007259:Infrared Rays; D008081:Liposomes / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
D008081:Liposomes; D011092:Polyethylene Glycols; D006046:Gold; D007208:Indocyanine Green
indocyanine green; light activation; liposome; macromolecules; molecular dynamics; triggered release