Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan.
Small. 2014 Nov;10(22):4785-95. doi: 10.1002/smll.201401559. Epub 2014 Aug 26.
An approach for enzyme therapeutics is elaborated with cell-implanted nanoreactors that are based on multiple enzymes encapsulated in hollow silica nanospheres (HSNs). The synthesis of HSNs is carried out by silica sol-gel templating of water-in-oil microemulsions so that polyethyleneimine (PEI) modified enzymes in aqueous phase are encapsulated inside the HSNs. PEI-grafted superoxide dismutase (PEI-SOD) and catalase (PEI-CAT) encapsulated in HSNs are prepared with quantitative control of the enzyme loadings. Excellent activities of superoxide dismutation by PEI-SOD@HSN are found and transformation of H2 O2 to water by PEI-CAT@HSN. When PEI-SOD and PEI-CAT are co-encapsulated, cascade transformation of superoxide through hydrogen peroxide to water was facile. Substantial fractions of HSNs exhibit endosome escape to cytosol after their delivery to cells. The production of downstream reactive oxygen species (ROS) and COX-2/p-p38 expression show that co-encapsulated SOD/CAT inside the HSNs renders the highest cell protection against the toxicant N,N'-dimethyl-4,4'-bipyridinium dichloride (paraquat). The rapid cell uptake and strong detoxification effect on superoxide radicals by the SOD/CAT-encapsulated hollow mesoporous silica nanoparticles demonstrate the general concept of implanting catalytic nanoreactors in biological cells with designed functions.
一种酶治疗方法是通过植入细胞的纳米反应器来实现的,该纳米反应器基于封装在中空硅纳米球(HSN)中的多种酶。HSN 的合成是通过水包油微乳液的硅溶胶-凝胶模板化来进行的,使得在水相中修饰的聚乙烯亚胺(PEI)酶被封装在 HSN 内部。PEI 接枝超氧化物歧化酶(PEI-SOD)和过氧化氢酶(PEI-CAT)被封装在 HSN 中,酶载量可以得到定量控制。发现封装在 HSN 中的 PEI-SOD 具有极好的超氧化物歧化酶活性,PEI-CAT@HSN 可以将 H2O2 转化为水。当 PEI-SOD 和 PEI-CAT 共封装时,通过过氧化氢将超氧化物转化为水的级联转化变得容易。将 HSN 递送到细胞后,大量 HSN 显示出从内涵体逃逸到细胞质的能力。下游活性氧(ROS)的产生和 COX-2/p-p38 的表达表明,共封装在 HSN 内的 SOD/CAT 可以最大限度地保护细胞免受有毒物质 N,N'-二甲基-4,4'-联吡啶二氯化物(百草枯)的侵害。SOD/CAT 封装的中空介孔硅纳米粒子具有快速的细胞摄取能力和对超氧自由基的强解毒作用,证明了在生物细胞中植入具有设计功能的催化纳米反应器的一般概念。