TY - JOUR
T1 - SOD1 nanozyme with reduced toxicity and MPS accumulation
AU - Jiang, Yuhang
AU - Arounleut, Phonepasong
AU - Rheiner, Steven
AU - Bae, Younsoo
AU - Kabanov, Alexander V.
AU - Milligan, Carol
AU - Manickam, Devika S.
N1 - Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/6/10
Y1 - 2016/6/10
N2 - We previously developed a "cage"-like nano-formulation (nanozyme) for copper/Zinc superoxide dismutase (SOD1) by polyion condensation with a conventional block copolymer poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) followed by chemical cross-linking. Herein we report a new SOD1 nanozyme based on PEG-b-poly(aspartate diethyltriamine) (PEG-PAsp(DET), or PEG-DET for short) engineered for chronic dosing. This new nanozyme was spherical (Rg/Rh = 0.785), and hollow (60% water composition) nanoparticles with colloidal properties similar to PLL-based nanozyme. It was better tolerated by brain microvessel endothelial/neuronal cells, and accumulated less in the liver and spleen. This formulation reduced the infarct volumes by more than 50% in a mouse model of ischemic stroke. However, it was not effective at preventing neuromuscular junction denervation in a mutant SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS). To our knowledge, this work is the first report of using PEG-DET for protein delivery and a direct comparison between two cationic block copolymers demonstrating the effect of polymer structure in modulating the mononuclear phagocyte system (MPS) accumulation of polyion complexes.
AB - We previously developed a "cage"-like nano-formulation (nanozyme) for copper/Zinc superoxide dismutase (SOD1) by polyion condensation with a conventional block copolymer poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) followed by chemical cross-linking. Herein we report a new SOD1 nanozyme based on PEG-b-poly(aspartate diethyltriamine) (PEG-PAsp(DET), or PEG-DET for short) engineered for chronic dosing. This new nanozyme was spherical (Rg/Rh = 0.785), and hollow (60% water composition) nanoparticles with colloidal properties similar to PLL-based nanozyme. It was better tolerated by brain microvessel endothelial/neuronal cells, and accumulated less in the liver and spleen. This formulation reduced the infarct volumes by more than 50% in a mouse model of ischemic stroke. However, it was not effective at preventing neuromuscular junction denervation in a mutant SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS). To our knowledge, this work is the first report of using PEG-DET for protein delivery and a direct comparison between two cationic block copolymers demonstrating the effect of polymer structure in modulating the mononuclear phagocyte system (MPS) accumulation of polyion complexes.
KW - ALS
KW - Antioxidant
KW - MPS
KW - Mouse
KW - PEG-PAsp(DET)
KW - PEG-PLL
KW - Protein delivery
KW - Stroke
KW - Superoxide dismutase
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=84977881912&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977881912&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.02.038
DO - 10.1016/j.jconrel.2016.02.038
M3 - Article
C2 - 26928528
AN - SCOPUS:84977881912
SN - 0168-3659
VL - 231
SP - 38
EP - 49
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -