Light induced cytosolic drug delivery from liposomes with gold nanoparticles

• Published in: Journal of controlled release 2015-04, Vol.203, p.85-98
• Main Authors: Lajunen, Tatu, Viitala, Lauri, Kontturi, Leena-Stiina, Laaksonen, Timo, Liang, Huamin, Vuorimaa-Laukkanen, Elina, Viitala, Tapani, Le Guével, Xavier, Yliperttula, Marjo, Murtomäki, Lasse, Urtti, Arto
• Format: Article
• Language: English
• Subjects: Cell Line; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - metabolism; Drug Liberation; Fluoresceins - administration & dosage; Fluorescent Dyes - administration & dosage; Gold - chemistry; Gold - metabolism; Hot Temperature; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen-Ion Concentration; Light; Liposomes - chemistry; Liposomes - metabolism; Metal Nanoparticles - chemistry; Retinal Pigment Epithelium - cytology; Retinal Pigment Epithelium - metabolism
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2015.02.028

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.