Versatile and efficient targeting using a single nanoparticulate platform: application to cancer and Alzheimer's disease.
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 β-amyloid peptide 1-42 (Aβ(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 Aβ(1-42) species comparatively to other kinds of colloidal systems and led to significant aggregation inhibition and toxicity rescue of Aβ(1-42) at low molar ratios.
Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Faculté de Pharmacie, University Paris-Sud, UMR CNRS 8612, 5 rue Jean-Baptiste Clément, F-92296 Châtenay-Malabry, France.
Benjamin
B
Le Droumaguet
Julien
J
Nicolas
Davide
D
Brambilla
Simona
S
Mura
Andrei
A
Maksimenko
Line
L
De Kimpe
Elisa
E
Salvati
Cristiano
C
Zona
Cristina
C
Airoldi
Mara
M
Canovi
Marco
M
Gobbi
Noiray
N
Magali
Barbara
B
La Ferla
Francesco
F
Nicotra
Wiep
W
Scheper
Orfeu
O
Flores
Massimo
M
Masserini
Karine
K
Andrieux
Patrick
P
Couvreur
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003102:Colloids; D003487:Cyanoacrylates / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D036103:Nanotechnology; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D010446:Peptide Fragments / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D017978:Receptors, Growth Factor / Q000378:metabolism; D020349:Surface Plasmon Resonance
D016229:Amyloid beta-Peptides; D003102:Colloids; D003487:Cyanoacrylates; D004337:Drug Carriers; D010446:Peptide Fragments; D011108:Polymers; D017978:Receptors, Growth Factor; C075222:amyloid beta-protein (1-42); C052136:biotin receptor