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Angew Chem Int Ed Engl. 2014 Aug 18;53(34):8975-9. doi: 10.1002/anie.201404766. Epub 2014 Jul 2.

Development of multinuclear polymeric nanoparticles as robust protein nanocarriers.

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Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA); MIT-Harvard Center for Cancer Nanotechnology Excellence, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA).


One limitation of current biodegradable polymeric nanoparticles is their inability to effectively encapsulate and sustainably release proteins while maintaining protein bioactivity. Here we report the engineering of PLGA-polycation nanoparticles with a core-shell structure that act as a robust vector for the encapsulation and delivery of proteins and peptides. The optimized nanoparticles can load high amounts of proteins (>20 % of nanoparticles by weight) in aqueous solution without organic solvents through electrostatic interactions by simple mixing, thereby forming nanospheres in seconds with diameters <200 nm. The relationship between nanosphere size, surface charge, PLGA-polycation composition, and protein loading is also investigated. The stable nanosphere complexes contain multiple PLGA-polycation nanoparticles, surrounded by large amounts of protein. This study highlights a novel strategy for the delivery of proteins and other relevant molecules.


nanoparticles; polycations; polymers; protein delivery; structure-function relationships

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