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鈥檚 disease (AD). Prepared by copper-catalyzed azide鈥揳lkyne 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 lig
ands that enabled specific targeting. The construction method is very versatile
and was illustrated by the coupling of a small library of lig
ands (
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 尾-amyloid peptide 1鈥?2 (A尾
1鈥?2), believed to be the most representative
and toxic species in AD, both under its monomeric
and fibrillar forms. In the case of AD, the lig
and-functionalized NPs exhibited higher affinity toward A尾
1鈥?2 species comparatively to other kinds of colloidal systems
and led to significant aggregation inhibition
and toxicity rescue of A尾
1鈥?2 at low molar ratios.
Keywords:
nanoparticles; poly(alkyl cyanoacrylate); Alzheimer鈥檚 disease; cancer; A尾 peptide; targeting