Development of Multinuclear Polymeric Nanoparticles as Robust Protein Nanocarriers

Authors

  • Dr. Jun Wu,

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

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

    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
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  • Lili Zhao,

    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
    2. School of Life Science, Nanjing University, Nanjing, Jiangsu, 210093 (P.R. China)
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  • Dr. Zeyu Xiao,

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

    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
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  • Rohit John,

    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
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  • Shaunak Ray,

    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
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  • Dr. Xiaoyang Xu,

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

    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
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  • Prof. Philip W. Kantoff,

    1. Lank Center for Genitourinary Oncology, Danan-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (USA)
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  • Prof. Omid C. Farokhzad

    Corresponding author
    1. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)
    2. MIT-Harvard Center for Cancer Nanotechnology Excellence, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
    3. King Abdulaziz University, Jeddah 22254 (Saudi Arabia)
    • Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA)

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  • This research was supported by the National Institutes of Health under grant numbers CA151884, HSSN268201000045C, and EB015419 as well as the David Koch-Prostate Cancer Foundation Program in Cancer Nanotherapeutics, Movember Challenge Award from Prostate Cancer Foundation and the National Research Foundation of Korea K1A1A2048701. O.C.F. has financial interest in BIND Therapeutics, Selecta Biosciences, and Blend Therapeutics, biopharmaceutical companies that are developing therapeutic nanoparticles. J.S. acknowledges the financial support from the NCI R00A160350 and PCF Young Investigator Award. X.X. acknowledges the financial support from the NIH National Research Service Award (NRSA) 1F32CA168163-03.

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.

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