[en] Despite significant advances in melanoma therapy, low response rates and multidrug resistance (MDR) have been described, reducing the anticancer efficacy of the administered molecules. Among the causes to explain these resistances, the decreased intratumoral pH is known to potentiate MDR and to reduce the sensitivity to anticancer molecules. Nanomedicines have been widely exploited as the carriers of MDR reversing molecules. Lipid nanocapsules (LNC) are nanoparticles that have already demonstrated their ability to improve cancer treatment. Here, LNC were modified with novel copolymers that combine N-vinylpyrrolidone (NVP) to impart stealth properties and vinyl imidazole (Vim), providing pH-responsive ability to address classical chemoresistance by improving tumor cell entry. These copolymers could be post-inserted at the LNC surface, leading to the property of going from neutral charge under physiological pH to positive charge under acidic conditions. LNC modified with polymer P5 (C18H37-P(NVP21-co-Vim15)) showed in vitro pH-responsive properties characterized by an enhanced cellular uptake under acidic conditions. Moreover, P5 surface modification led to an increased biological effect by protecting the nanocarrier from opsonization by complement activation. These data suggest that pH-sensitive LNC responds to what is expected from a promising nanocarrier to target metastatic melanoma
Research Center/Unit :
Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Belgium Center for Education and Research on Macromolecules (CERM), Belgium
Disciplines :
Materials science & engineering Chemistry
Author, co-author :
Pautu, Vincent; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium > University of Angers, Inserm, The National Center for Scientific Research (CNRS), Micro & Nanomedecines Translationnelles (MINT), France
Lepeltier, Elise; University of Angers, Inserm, The National Center for Scientific Research (CNRS), Micro & Nanomedecines Translationnelles (MINT), France
Mellinger, Adélie; University of Angers, Inserm, The National Center for Scientific Research (CNRS), Micro & Nanomedecines Translationnelles (MINT), France
Riou, Jérémie; University of Angers, Inserm, The National Center for Scientific Research (CNRS), Micro & Nanomedecines Translationnelles (MINT), France
Debuigne, Antoine ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium
Jérôme, Christine ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium
Clere, Nicolas; University of Angers, Inserm, The National Center for Scientific Research (CNRS), Micro & Nanomedecines Translationnelles (MINT), France
Passirani, Catherine; University of Angers, Inserm, The National Center for Scientific Research (CNRS), Micro & Nanomedecines Translationnelles (MINT), France
Language :
English
Title :
pH‐Responsive lipid nanocapsules: a promising strategy for improved resistant melanoma cell internalization
Publication date :
01 May 2021
Journal title :
Cancers
eISSN :
2072-6694
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
F.R.S.-FNRS - Fonds de la Recherche Scientifique LNCC - Ligue Nationale Contre le Cancer COST - European Cooperation in Science and Technology
Funding text :
Funding: This research was funded by La Ligue contre le Cancer—Comité de Maine et Loire.
Acknowledgments: This article is based upon work from COST Action STRATAGEM, CA17104, supported by the European Cooperation in Science and Technology (COST) and we thank them.
The authors would like to thank the Erasmus Mundus NANOFAR program and the Région Pays de la Loire (V.P.). A.D. is Senior Researcher Associate by the FRS‐FNRS (Belgium). Authors also thank SFR ICAT, Catherine Guillet from the “Plateforme d’Analyse Cellulaire et Moléculaire” (PACeM, Angers, France) for their expertise in the field of flow cytometry and Rodolphe Perrot
from the “Service Commun Imagerie et d’Analyse Microscopique” (SCIAM, Angers, France), for
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