Comparison of different cationized proteins as biomaterials for nanoparticle-based ocular gene delivery

• Cationized proteins were used for nanoparticulate ocular gene delivery.
• Albumin, gelatin and atelocollagen were cationized with spermine or ethylenediamine.
• Nanoparticle formation as well toxicity and siRNA/pDNA delivery was investigated.
• The ability to form stable nanoparticles was dependent of the molecular weight.
• The biological activity was dependent on molecular weight and type of amine used.

Cationized polymers have been proposed as transfection agents for gene therapy. The present work aims to improve the understanding of the potential use of different cationized proteins (atelocollagen, albumin and gelatin) as nanoparticle components and to investigate the possibility of modulating the physicochemical properties of the resulting nanoparticle carriers by selecting specific protein characteristics in an attempt to improve current ocular gene-delivery approaches. The toxicity profiles, as well as internalization and transfection efficiency, of the developed nanoparticles can be modulated by modifying the molecular weight of the selected protein and the amine used for cationization. The most promising systems are nanoparticles based on intermediate molecular weight gelatin cationized with the endogenous amine spermine, which exhibit an adequate toxicological profile, as well as effective association and protection of pDNA or siRNA molecules, thereby resulting in higher transfection efficiency and gene silencing than the other studied formulations.

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