Versatile and Efficient Targeting Using a Single Nanoparticulate Platform: Application to Cancer and Alzheimer’s Disease

• Published in: ACS nano 2012-07, Vol.6 (7), p.5866-5879
• Main Authors: Le Droumaguet, Benjamin, Nicolas, Julien, Brambilla, Davide, Mura, Simona, Maksimenko, Andrei, De Kimpe, Line, Salvati, Elisa, Zona, Cristiano, Airoldi, Cristina, Canovi, Mara, Gobbi, Marco, Magali, Noiray, La Ferla, Barbara, Nicotra, Francesco, Scheper, Wiep, Flores, Orfeu, Masserini, Massimo, Andrieux, Karine, Couvreur, Patrick
• Format: Article
• Language: English
• Subjects: Affinity; Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Biodegradability; Biological effects; Cancer; Cell Line, Tumor; Colloids; Cyanoacrylates - chemistry; Drug Carriers - chemistry; Drug Delivery Systems; Galenic pharmacology; Humans; Life Sciences; Mice; Microscopy, Confocal; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoparticles - toxicity; Nanostructure; Nanotechnology; Neoplasms - diagnosis; Neoplasms - metabolism; Neoplasms - therapy; Peptide Fragments - metabolism; Pharmaceutical sciences; Platforms; Polymers - chemistry; Receptors, Growth Factor - metabolism; Self assembly; Surface Plasmon Resonance
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/nn3004372

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 (Aβ1–42), 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 Aβ1–42 species comparatively to other kinds of colloidal systems and led to significant aggregation inhibition and toxicity rescue of Aβ1–42 at low molar ratios.