TY - JOUR
T1 - Versatile and Efficient Targeting Using a Single Nanoparticulate Platform: Application to Cancer and Alzheimer's Disease
T2 - Application to cancer and alzheimer's disease
AU - Le Droumaguet, Benjamin
AU - Nicolas, Julien
AU - Brambilla, Davide
AU - Mura, Simona
AU - Maksimenko, Andrei
AU - de Kimpe, Line
AU - Salvati, Elisa
AU - Zona, Cristiano
AU - Airoldi, Cristina
AU - Canovi, Mara
AU - Gobbi, Marco
AU - Magali, Noiray
AU - La Ferla, Barbara
AU - Nicotra, Francesco
AU - Scheper, Wiep
AU - Flores, Orfeu
AU - Masserini, Massimo
AU - Andrieux, Karine
AU - Couvreur, Patrick
PY - 2012/7/24
Y1 - 2012/7/24
N2 - A versatile and efficient functionalization strategy for polymeric nanoparticles (NPs) has been reported and successfully applied to PEGylated, biodegradable poly(alkyl cyanoacrylate) (PACA) nanocarriers. The relevance of this platform was demonstrated in both the fields of cancer and Alzheimer's disease (AD). Prepared by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and subsequent self-assembly in aqueous solution of amphiphilic copolymers, the resulting functionalized polymeric NPs exhibited requisite characteristics for drug delivery purposes: (i) a biodegradable core made of poly(alkyl cyanoacrylate), (ii) a hydrophilic poly(ethylene glycol) (PEG) outer shell leading to colloidal stabilization, (iii) fluorescent properties provided by the covalent linkage of a rhodamine B-based dye to the polymer backbone, and (iv) surface functionalization with biologically active ligands that enabled specific targeting. The construction method is very versatile and was illustrated by the coupling of a small library of ligands (e.g., biotin, curcumin derivatives, and antibody), resulting in high affinity toward (i) murine lung carcinoma (M109) and human breast cancer (MCF7) cell lines, even in a coculture environment with healthy cells and (ii) the beta-amyloid peptide 1-42 (A beta(1-42)), believed to be the most representative and toxic species in AD, both under its monomeric and fibrillar forms. In the case of AD, the ligand-functionalized NPs exhibited higher affinity toward A beta(1-42) species comparatively to other kinds of colloidal systems and led to significant aggregation inhibition and toxicity rescue of A beta(1-42) at low molar ratios
AB - A versatile and efficient functionalization strategy for polymeric nanoparticles (NPs) has been reported and successfully applied to PEGylated, biodegradable poly(alkyl cyanoacrylate) (PACA) nanocarriers. The relevance of this platform was demonstrated in both the fields of cancer and Alzheimer's disease (AD). Prepared by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and subsequent self-assembly in aqueous solution of amphiphilic copolymers, the resulting functionalized polymeric NPs exhibited requisite characteristics for drug delivery purposes: (i) a biodegradable core made of poly(alkyl cyanoacrylate), (ii) a hydrophilic poly(ethylene glycol) (PEG) outer shell leading to colloidal stabilization, (iii) fluorescent properties provided by the covalent linkage of a rhodamine B-based dye to the polymer backbone, and (iv) surface functionalization with biologically active ligands that enabled specific targeting. The construction method is very versatile and was illustrated by the coupling of a small library of ligands (e.g., biotin, curcumin derivatives, and antibody), resulting in high affinity toward (i) murine lung carcinoma (M109) and human breast cancer (MCF7) cell lines, even in a coculture environment with healthy cells and (ii) the beta-amyloid peptide 1-42 (A beta(1-42)), believed to be the most representative and toxic species in AD, both under its monomeric and fibrillar forms. In the case of AD, the ligand-functionalized NPs exhibited higher affinity toward A beta(1-42) species comparatively to other kinds of colloidal systems and led to significant aggregation inhibition and toxicity rescue of A beta(1-42) at low molar ratios
U2 - https://doi.org/10.1021/nn3004372
DO - https://doi.org/10.1021/nn3004372
M3 - Article
C2 - 22725248
SN - 1936-0851
VL - 6
SP - 5866
EP - 5879
JO - ACS nano
JF - ACS nano
IS - 7
ER -