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Ligand-modified human serum albumin nanoparticles for enhanced gene delivery

: Look, J.; Wilhelm, N.; Briesen, H. von; Noske, N.; Günther, C.; Langer, K.; Gorjup, E.


Molecular pharmaceutics 12 (2015), Nr.9, S.3202-3213
ISSN: 1543-8384
ISSN: 1543-8392
Bundesministerium für Bildung und Forschung BMBF
Bundesministerium für Bildung und Forschung BMBF
Bundesministerium für Bildung und Forschung BMBF
Fraunhofer IBMT ()

The development of nonviral gene delivery systems is a great challenge to enable safe gene therapy. In this study, ligand-modified nanopartides based on human serum albumin (HSA) were developed and optimized for an efficient gene therapy. Different glutaraldehyde cross-linking degrees were investigated to optimize the HSA nanopartides for gene delivery. The peptide sequence arginine-glycine-aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are well-known as promising targeting ligands. Plasmid DNA loaded HSA nanopartides were covalently modified on their surface with these different ligands. The transfection potential of the obtained plasmid DNA loaded RGD-and Tat-modified nanopartides was investigated in vitro, and optimal incubation conditions for these preparations were studied. It turned out that Tat-modified HSA nanopartides with the lowest cross-linking degree of 20% showed the highest transfection potential. Taken together, ligand-functionalized represent promising tools for efficient and safe gene therapy. HSA nanopartides