title: Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model.
abstract: Liposomal drug delivery vehicles are promising nanomedicine tools for bringing cytotoxic drugs to cancerous tissues selectively. However, the triggered cargo release from liposomes in response to a target-specific stimulus has remained elusive. We report on functionalizing stealth-liposomes with an engineered ion channel and using these liposomes in vivo for releasing an imaging agent into a cerebral glioma rodent model. If the ambient pH drops below a threshold value, the channel generates temporary pores on the liposomes, thus allowing leakage of the intraluminal medicines. By using magnetic resonance spectroscopy and imaging, we show that engineered liposomes can detect the mildly acidic pH of the tumor microenvironment with 0.2 pH unit precision and they release their content into C6 glioma tumors selectively, in vivo. A drug delivery system with this level of sensitivity and selectivity to environmental stimuli may well serve as an optimal tool for environmentally-triggered and image-guided drug release.
  
  
  BACKGROUND
  Cancer remains a leading cause of mortality worldwide. With advances in science, delivery systems of anti-cancer drugs have also become sophisticated. In this article, the authors designed and characterized functionalized liposomal vehicles, which would release the drug payload in a highly sensitive manner in response to a change in pH environment in an animal glioma model. The novel data would enable better future designs of drug delivery systems.
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC/UAM, c/ Arturo Duperier 4, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pacheco-Torres
authors.affiliation: Groningen Institute of Biomolecular Sciences and Biotechnology, University of Groningen, Nijenborgh 4, AG Groningen, The Netherlands.
authors.forename: Nobina
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Institute of Chemistry, Faculty of Science, P.J. Safarik University in Kosice, Moyzesova 11, Kosice, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Walko
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC/UAM, c/ Arturo Duperier 4, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Larrubia
authors.affiliation: Laboratory of Organic Synthesis and Molecular Imaging by MRI, Faculty of Sciences UNED, CSIC Associated Unit, Paseo Senda del Rey 9, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Ballesteros
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC/UAM, c/ Arturo Duperier 4, Madrid, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cerdan
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Neuroscience, Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands. Electronic address: a.kocer@umcg.nl.
authors.forename: Armagan
authors.initials: A
authors.lastname: Kocer
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005909:Glioblastoma / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004337:Drug Carriers; D007473:Ion Channels; D008081:Liposomes
keywords: C6 glioma tumors; Ion channel engineering; Magnetic resonance spectroscopy and imaging; Mechanosensitive channel of large conductance; Triggered drug delivery; pH-sensitive liposomes