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纳米氧化铈:代谢相互作用及通过聚乳酸-羟基乙酸共聚物包封实现递送

Nanoceria: Metabolic interactions and delivery through PLGA-encapsulation.

作者信息

Mehta Apoorva, Scammon Bradley, Shrake Kevin, Bredikhin Mikhail, Gil Dmitry, Shekunova Taisiya, Baranchikov Alexander, Ivanov Vladimir, Reukov Vladimir

机构信息

Department of Bioengineering, Clemson University, 301 Rhodes Hall, Clemson, SC 29634, USA.

Department of Orthopaedics, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA; Department of Orthopaedic Surgery, Harvard Medical School, Harvard University, Boston, MA 02115, USA.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Sep;114:111003. doi: 10.1016/j.msec.2020.111003. Epub 2020 Apr 23.

Abstract

Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating damage from burns, radiation, and bacterial infection. This mitigating activity is analogous to that property of metabolic enzymes such as superoxide dismutase (SOD) and catalase - scavengers of reactive oxygen species (ROS). Therefore, nanoceria can protect cells from environmental oxidative stress. This therapeutic effect prompted studies of nanoceria and metabolic enzymes as a combination therapy. The activity and structure of SOD, catalase, and lysozyme were examined in the presence of nanoceria. A complementary relationship between SOD and nanoceria motivated the present work, in which we explored a method for simultaneous delivery of SOD and nanoceria. The biocompatibility and tunable degradation of poly(lactic-co-glycolic acid) (PLGA) made it a candidate material for encapsulating both nanoceria and SOD. Cellular uptake studies were conducted along with a cytotoxicity assay. The antioxidative properties of PLGA-nanoceria-SOD particles were verified by adding HO to cell culture and imaging with fluorescent markers of oxidative stress. Our results suggest that PLGA is a suitable encapsulating carrier for simultaneous delivering nanoceria and SOD together, and that this combination effectively reduces oxidative stress in vitro.

摘要

氧化铈纳米颗粒(纳米氧化铈)具有可循环的抗氧化活性。它在生物医学工程领域有众多潜在应用,比如减轻烧伤、辐射和细菌感染造成的损伤。这种减轻损伤的活性类似于超氧化物歧化酶(SOD)和过氧化氢酶等代谢酶的特性——活性氧物质(ROS)的清除剂。因此,纳米氧化铈可以保护细胞免受环境氧化应激的影响。这种治疗效果促使人们对纳米氧化铈和代谢酶进行联合治疗的研究。在纳米氧化铈存在的情况下,对SOD、过氧化氢酶和溶菌酶的活性及结构进行了检测。SOD与纳米氧化铈之间的互补关系推动了本研究工作,我们探索了一种同时递送SOD和纳米氧化铈的方法。聚乳酸-羟基乙酸共聚物(PLGA)的生物相容性和可调节降解性使其成为一种用于封装纳米氧化铈和SOD的候选材料。进行了细胞摄取研究以及细胞毒性测定。通过向细胞培养物中添加过氧化氢并用氧化应激荧光标记物成像,验证了PLGA-纳米氧化铈-SOD颗粒的抗氧化特性。我们的结果表明,PLGA是一种适合同时递送纳米氧化铈和SOD的封装载体,并且这种组合能有效减轻体外氧化应激。

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