Versatile and Efficient Targeting Using a Single Nanoparticulate Platform and its Application to Cancer and Alzheimer's Disease

A versatile and efficient functionalization strategy of polymeric nanoparticles 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). Based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) and concomitant self-assembly in aqueous solution of amphiphilic copolymers, the resulting functionalized polymeric nanoparticles 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, curcumine derivatives and antibody), resulting in high affinity towards: (i) murine lung carcinoma (M109) and human breast cancer (MCF7) cell lines, (ii) the β-amyloid peptide 1-42 (Aβ1-42), believed to be the most representative and toxic species in AD, and (iii) Aβ1-42 fibrils, usually located in AD brains. 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. This new functional synthetic tool may open an avenue towards efficient cell targeting for a broad variety of diseases, which is still an active challenge in the field due to the lack of appropriate nanoparticulate systems gathering all the required features.