TY - JOUR
T1 - Application of an assay Cascade methodology for a deep preclinical characterization of polymeric nanoparticles as a treatment for gliomas
AU - Fornaguera, Cristina
AU - Lázaro, Miguel Ángel
AU - Brugada-Vilà, Pau
AU - Porcar, Irene
AU - Morera, Ingrid
AU - Guerra-Rebollo, Marta
AU - Garrido, Cristina
AU - Rubio, Núria
AU - Blanco, Jerónimo
AU - Cascante, Anna
AU - Borrós, Salvador
N1 - Funding Information:
Financial support from MINECO/FEDER (grants RTC-2015-3751-1, SAF2015-64927-C2-1-R and SAF2015-64927-C2-2-R) and Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Terapia Celular-TERCEL) are acknowledged. Cristina Fornaguera is grateful to MINECO for the Postdoctoral Fellowship (grant Torres Quevedo 2016).
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/2/7
Y1 - 2018/2/7
N2 - Glioblastoma multiforme (GBM) is the most devastating primary brain tumor due to its infiltrating and diffuse growth characteristics, a situation compounded by the lack of effective treatments. Currently, many efforts are being devoted to find novel formulations to treat this disease, specifically in the nanomedicine field. However, due to the lack of comprehensive characterization that leads to insufficient data on reproducibility, only a reduced number of nanomedicines have reached clinical phases. In this context, the aim of the present study was to use a cascade of assays that evaluate from physical-chemical and structural properties to biological characteristics, both in vitro and in vivo, and also to check the performance of nanoparticles for glioma therapy. An amphiphilic block copolymer, composed of polyester and poly(ethylene glycol; PEG) blocks, has been synthesized. Using a mixture of this copolymer and a polymer containing an active targeting moiety to the Blood Brain Barrier (BBB; Seq12 peptide), biocompatible and biodegradable polymeric nanoparticles have been prepared and extensively characterized. In vitro studies demonstrated that nanoparticles are safe for normal cells but cytotoxic for cancer cells. In vivo studies in mice demonstrated the ability of the Seq12 peptide to cross the BBB. Finally, in vivo efficacy studies using a human tumor model in SCID mice resulted in a significant 50% life-span increase, as compared with non-treated animals. Altogether, this assay cascade provided extensive pre-clinical characterization of our polymeric nanoparticles, now ready for clinical evaluation.
AB - Glioblastoma multiforme (GBM) is the most devastating primary brain tumor due to its infiltrating and diffuse growth characteristics, a situation compounded by the lack of effective treatments. Currently, many efforts are being devoted to find novel formulations to treat this disease, specifically in the nanomedicine field. However, due to the lack of comprehensive characterization that leads to insufficient data on reproducibility, only a reduced number of nanomedicines have reached clinical phases. In this context, the aim of the present study was to use a cascade of assays that evaluate from physical-chemical and structural properties to biological characteristics, both in vitro and in vivo, and also to check the performance of nanoparticles for glioma therapy. An amphiphilic block copolymer, composed of polyester and poly(ethylene glycol; PEG) blocks, has been synthesized. Using a mixture of this copolymer and a polymer containing an active targeting moiety to the Blood Brain Barrier (BBB; Seq12 peptide), biocompatible and biodegradable polymeric nanoparticles have been prepared and extensively characterized. In vitro studies demonstrated that nanoparticles are safe for normal cells but cytotoxic for cancer cells. In vivo studies in mice demonstrated the ability of the Seq12 peptide to cross the BBB. Finally, in vivo efficacy studies using a human tumor model in SCID mice resulted in a significant 50% life-span increase, as compared with non-treated animals. Altogether, this assay cascade provided extensive pre-clinical characterization of our polymeric nanoparticles, now ready for clinical evaluation.
KW - Glioblastoma multiforme
KW - NCL assay cascade protocol
KW - Nanoparticle preclinical characterization
KW - Paclitaxel
KW - Polymeric nanoparticles
KW - Research lab results translation
UR - http://www.scopus.com/inward/record.url?scp=85048730584&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000424503700001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1080/10717544.2018.1436099
DO - 10.1080/10717544.2018.1436099
M3 - Article
C2 - 29412012
AN - SCOPUS:85048730584
SN - 1071-7544
VL - 25
SP - 472
EP - 483
JO - Drug Delivery
JF - Drug Delivery
IS - 1
ER -