2024-03-29T01:03:56Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1249982021-10-27T07:10:07Zcom_10261_22com_10261_1col_10261_275
Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model
Pacheco-Torres, Jesús
Mukherjee, Nobina
Walko, Martin
López-Larrubia, Pilar
Ballesteros, Paloma
Cerdán, Sebastián
Kocer, Armagan
Ministerio de Economía y Competitividad (España)
Ministerio de Educación y Ciencia (España)
Netherlands Organization for Scientific Research
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas (España)
Comunidad de Madrid
European Research Council
European Commission
C6 glioma tumors
Triggered drug delivery
Ion channel engineering
Mechanosensitive channel of large conductance
pH-sensitive liposomes
Magnetic resonance spectroscopy and imaging
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 Editor: 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
This work was supported in part by grants SAF-2008-01327, SAF2011-23622 and S2010/BMD-2349 to SC, grants CTQ-2010-20960 and CTQ-2013-47669-R to P.B. and P.L.L. and, grants European Research Council-Ideas Program Starting Grant 208814, ERC-Proof of concept Grant (MOCHA), and the Netherlands Organization for Scientific Research Grant (NWO-VIDI)
700.57.427 to A.K, MEDITRANS (NMP4-CT-2006-026668) to A.K., S.C., P.B. and N.M-. J.P-T received a predoctoral contract from CSIC.
Peer Reviewed
2015-11-13T11:02:59Z
2015-11-13T11:02:59Z
2015
2015-11-13T11:03:00Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1016/j.nano.2015.03.014
issn: 1549-9634
Nanomedicine: Nanotechnology, Biology, and Medicine 11(6): 1345-1354 (2015)
http://hdl.handle.net/10261/124998
10.1016/j.nano.2015.03.014
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100000781
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/100012818
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info:eu-repo/grantAgreement/EC/FP7/208814
S2010/BMD-2349/I2M2
info:eu-repo/grantAgreement/EC/FP7/310627
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2013-47669-R
Sí
none
Elsevier