Light induced cytosolic drug delivery from liposomes with gold nanoparticles Tatu Lajunen a, ⁎ ,1 , Lauri Viitala b , Leena-Stiina Kontturi a , Timo Laaksonen a , Huamin Liang c , Elina Vuorimaa-Laukkanen c , Tapani Viitala a , Xavier Le Guével d , Marjo Yliperttula a , Lasse Murtomäki b , Arto Urtti a,e a Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, FI-00014, Helsinki, Finland b Department of Chemistry, Aalto University, P.O. Box 16100, FI-00076 Aalto, Finland c Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere, Finland d The Andalusian Centre for Nanomedicine and Biotechnology, Parque Tecnológico de Andalucía c/ Severo Ochoa 35, 29590 Campanillas, Málaga, Spain e School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland abstract article info Article history: Received 18 December 2014 Received in revised form 11 February 2015 Accepted 17 February 2015 Available online 19 February 2015 Chemical compounds studied in this article: 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (PubChem CID: 6138) 1,2-Distearoyl-sn-glycero-3-phosphocholine (PubChem CID: 94190) 1-Stearoyl-2-hydroxy-sn-glycero-3- phosphocholine (PubChem CID: 497299) 1,2-Distearoyl-sn-glycero-3- phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (PubChem CID: 86278269) 1,3-Diolein (PubChem CID: 33120) Cholesteryl hemisuccinate (PubChem CID: 65082) Calcein (PubChem CID: 65079) Gold (PubChem CID: 23985) Keywords: Light activation Liposome Gold nanoparticle Intracellular delivery Triggered release Retinal pigment epithelium 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 tempera- ture increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to devel- op 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 re- leased 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. © 2015 Elsevier B.V. All rights reserved. Journal of Controlled Release 203 (2015) 85–98 ⁎ Corresponding author at: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 9), FI-00014 Helsinki, Finland. E-mail addresses: tatu.lajunen@helsinki.fi (T. Lajunen), lauri.viitala@aalto.fi (L. Viitala), leena.kontturi@helsinki.fi (L.-S. Kontturi), timo.laaksonen@helsinki.fi (T. Laaksonen), huamin.liang@tut.fi (H. Liang), elina.vuorimaa@tut.fi (E. Vuorimaa-Laukkanen), tapani.viitala@helsinki.fi (T. Viitala), xleguevel@bionand.es (X. Le Guével), marjo.yliperttula@helsinki.fi (M. Yliperttula), lasse.murtomaki@aalto.fi (L. Murtomäki), arto.urtti@helsinki.fi (A. Urtti). 1 Present address: (Until 31st of March 2015) Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. http://dx.doi.org/10.1016/j.jconrel.2015.02.028 0168-3659/© 2015 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel