Development of Multinuclear Polymeric Nanoparticles as Robust Protein Nanocarriers

被引:136
作者
Wu, Jun [1 ,2 ]
Kamaly, Nazila [1 ,2 ]
Shi, Jinjun [1 ]
Zhao, Lili [1 ,4 ]
Xiao, Zeyu [1 ,2 ]
Hollett, Geoffrey [1 ]
John, Rohit [1 ]
Ray, Shaunak [1 ]
Xu, Xiaoyang [1 ,2 ]
Zhang, Xueqing [1 ]
Kantoff, Philip W. [5 ]
Farokhzad, Omid C. [1 ,2 ,3 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA
[2] MIT, MIT Harvard Ctr Canc Nanotechnol Excellence, Cambridge, MA 02139 USA
[3] King Abdulaziz Univ, Jeddah 22254, Saudi Arabia
[4] Nanjing Univ, Sch Life Sci, Nanjing 210093, Jiangsu, Peoples R China
[5] Harvard Univ, Sch Med, Danan Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA
基金
美国国家卫生研究院; 新加坡国家研究基金会;
关键词
nanoparticles; polycations; polymers; protein delivery; structure-function relationships; HYBRID NANOPARTICLES; DELIVERY; HYDROGELS; MICROSPHERES; TRANSLATION; RELEASE; BIOLOGY; ERA;
D O I
10.1002/anie.201404766
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:8975 / 8979
页数:5
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