title: Light induced cytosolic drug delivery from liposomes with gold nanoparticles.
abstract: Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells.
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland. Electronic address: tatu.lajunen@helsinki.fi.
authors.forename: Tatu
authors.initials: T
authors.lastname: Lajunen
authors.affiliation: Department of Chemistry, Aalto University, P.O. Box 16100, FI-00076 Aalto, Finland. Electronic address: lauri.viitala@aalto.fi.
authors.forename: Lauri
authors.initials: L
authors.lastname: Viitala
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland. Electronic address: leena.kontturi@helsinki.fi.
authors.forename: Leena-Stiina
authors.initials: LS
authors.lastname: Kontturi
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland. Electronic address: timo.laaksonen@helsinki.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.affiliation: Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere, Finland. Electronic address: huamin.liang@tut.fi.
authors.forename: Huamin
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere, Finland. Electronic address: elina.vuorimaa@tut.fi.
authors.forename: Elina
authors.initials: E
authors.lastname: Vuorimaa-Laukkanen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland. Electronic address: tapani.viitala@helsinki.fi.
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.affiliation: The Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnológico de Andalucía c/ Severo Ochoa 35, 29590 Campanillas, Málaga, Spain. Electronic address: xleguevel@bionand.es.
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Guével
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland. Electronic address: marjo.yliperttula@helsinki.fi.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.affiliation: Department of Chemistry, Aalto University, P.O. Box 16100, FI-00076 Aalto, Finland. Electronic address: lasse.murtomaki@aalto.fi.
authors.forename: Lasse
authors.initials: L
authors.lastname: Murtomäki
authors.affiliation: 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. Electronic address: arto.urtti@helsinki.fi.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
mesh_terms: D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D005452:Fluoresceins / Q000008:administration & dosage*; D005456:Fluorescent Dyes / Q000008:administration & dosage*; D006046:Gold / Q000737:chemistry* / Q000378:metabolism; D006358:Hot Temperature; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D006046:Gold; C007740:fluorexon
keywords: 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (PubChem CID: 6138); 1,2-Distearoyl-sn-glycero-3-phosphocholine (PubChem CID: 94190); 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PubChem CID: 86278269); 1,3-Diolein (PubChem CID: 33120); 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (PubChem CID: 497299); Calcein (PubChem CID: 65079); Cholesteryl hemisuccinate (PubChem CID: 65082); Gold (PubChem CID: 23985); Gold nanoparticle; Intracellular delivery; Light activation; Liposome; Retinal pigment epithelium; Triggered release