TY - JOUR
T1 - Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model
AU - Pacheco-Torres, J.
AU - Mukherjee, N.
AU - Walko, M.
AU - López-Larrubia, P.
AU - Ballesteros, P.
AU - Cerdan, S.
AU - Kocer, A.
PY - 2015
Y1 - 2015
N2 - 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.From the Clinical EditorCancer 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.Graphical abstractAn engineered ion channel embedded in a drug-delivery liposome detects the pH differences in the range of 7.0 and 6.6, within a brain tumor in mice and releases the liposomal content, e.g. an imaging agent, only at low pH areas.
AB - 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.From the Clinical EditorCancer 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.Graphical abstractAn engineered ion channel embedded in a drug-delivery liposome detects the pH differences in the range of 7.0 and 6.6, within a brain tumor in mice and releases the liposomal content, e.g. an imaging agent, only at low pH areas.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84937145710&partnerID=MN8TOARS
U2 - 10.1016/j.nano.2015.03.014
DO - 10.1016/j.nano.2015.03.014
M3 - Article
SN - 1549-9634
VL - 11
SP - 1345
EP - 1354
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 6
ER -