Versatile and Efficient Targeting Using a Single Nanoparticulate Platform: Application to Cancer and Alzheimer鈥檚 Disease
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- 作者：Benjamin Le Droumaguet ; Julien Nicolas ; Davide Brambilla ; Simona Mura ; Andrei Maksimenko ; Line De Kimpe ; Elisa Salvati ; Cristiano Zona ; Cristina Airoldi ; Mara Canovi ; Marco Gobbi ; Magali Noiray ; Barbara La Ferla ; Francesco Nicotra ; Wiep Scheper ; Orfeu Flores ; Massimo Masserini ; Karine Andrieux ; Patrick Couvreur
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：July 24, 2012
- 年：2012
- 卷：6
- 期：7
- 页码：5866-5879
- 全文大小：808K
- 年卷期：v.6,no.7(July 24, 2012)
- ISSN：1936-086X
文摘
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 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 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 ligand-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.