title: Development of multinuclear polymeric nanoparticles as robust protein nanocarriers.
abstract: 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.
authors.affiliation: 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).
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Nazila
authors.initials: N
authors.lastname: Kamaly
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shi
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Xiao
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hollett
authors.forename: Rohit
authors.initials: R
authors.lastname: John
authors.forename: Shaunak
authors.initials: S
authors.lastname: Ray
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Xu
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
mesh_terms: D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D011108:Polymers; D011506:Proteins
keywords: nanoparticles; polycations; polymers; protein delivery; structure-function relationships