Cross-linked antioxidant nanozymes for improved delivery to CNS.
Cross-linked antioxidant nanozymes for improved delivery to CNS.
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DOI：
10.1016/j.nano.2011.05.010
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发表时间：
2012-01
影响因子：
5.4
通讯作者：
Kabanov, Alexander V.
中科院分区：
文献类型：
--
作者：
Klyachko, Natalia L.;Manickam, Devika S.;Brynskikh, Anna M.;Uglanova, Svetlana V.;Li, Shu;Higginbotham, Sheila M.;Bronich, Tatiana K.;Batrakova, Elena V.;Kabanov, Alexander V.
抗氧化酶、超氧化物歧化酶 1（SOD1，也称为 Cu/Zn SOD）和过氧化氢酶的制剂通过酶与阳离子嵌段共聚物、聚乙烯亚胺-聚（乙二醇）或聚（L-赖氨酸）-聚（乙二醇）的静电偶联来制备，然后通过共价交联来稳定 纳米颗粒。研究了不同的交联策略（使用戊二醛、双（磺基琥珀酰亚胺基）辛二酸钠盐或 1-乙基-3-[3-二甲基氨基丙基]碳二亚胺盐酸盐与 N-羟基磺基琥珀酰亚胺）和反应条件（pH 值和聚阳离子/蛋白质电荷比），以固定活性酶 交联的纳米颗粒，称为“纳米酶”。还配制了含有 SOD1 和过氧化氢酶的双酶纳米颗粒。使用变性凝胶电泳和蛋白质印迹证实复合物的形成，并使用动态光散射和原子力显微镜进行物理化学表征。对小鼠进行的 125I 标记的含 SOD1 纳米酶的体内研究表明，与非交联复合物和天然 SOD1 相比，其在血液和大脑中的稳定性增加，并且在脑组织中的积累增加。未来的研究将评估这些制剂将抗氧化酶输送到中枢神经系统以减轻与神经系统疾病相关的氧化应激的潜力。
Formulations of antioxidant enzymes, superoxide dismutase 1 (SOD1, also known as Cu/Zn SOD) and catalase were prepared by electrostatic coupling of enzymes with cationic block copolymers, polyethyleneimine-poly(ethylene glycol) or poly(L-lysine)-poly(ethylene glycol), followed by covalent cross-linking to stabilize nanoparticles. Different cross-linking strategies (using glutaraldehyde, bis-(sulfosuccinimidyl)suberate sodium salt or 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride with N-hydroxysulfosuccinimide) and reaction conditions (pH and polycation/protein charge ratio) were investigated that allowed immobilizing active enzymes in cross-linked nanoparticles, termed “nanozymes”. Bi-enzyme nanoparticles, containing both SOD1 and catalase were also formulated. Formation of complexes was confirmed using denaturing gel electrophoresis and western blotting and physicochemical characterization was conducted using dynamic light scattering and atomic force microscopy. In vivo studies of 125I-labeled SOD1-containing nanozymes in mice demonstrated its increased stability in both blood and brain and increased accumulation in brain tissues, compared to non-cross-linked complexes and native SOD1. Future studies will evaluate potential of these formulations for delivery of antioxidant enzymes to central nervous system to attenuate oxidative stress associated with neurological diseases.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
4.8
作者：
Lyubchenko, Yuri L.;Shlyakhtenko, Luda S.
通讯作者：
Shlyakhtenko, Luda S.
影响因子：
10.8
作者：
Dziubla, TD;Karim, A;Muzykantov, VR
通讯作者：
Muzykantov, VR
DOI：
10.1007/978-1-60327-015-1_21
发表时间：
2009-01-01
期刊：
DNA-PROTEIN INTERACTIONS: PRINCIPLES AND PROTOCOLS, THIRD EDITION
影响因子：
--
作者：
Lyubchenko, Yuri L.;Shlyakhtenko, Luda S.;Gall, Alexander A.
通讯作者：
Gall, Alexander A.
影响因子：
4.7
作者：
Batrakova, Elena V.;Li, Shu;Gendelman, Howard E.
通讯作者：
Gendelman, Howard E.