Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University , Tallahassee, Florida 32310, United States.
Department of Biomedical Sciences, College of Medicine, Florida State University , Tallahassee, Florida 32306, United States.
Langmuir. 2016 Dec 20;32(50):13386-13393. doi: 10.1021/acs.langmuir.6b03160. Epub 2016 Dec 6.
Enzymes have been used to treat various human diseases and traumas. However, the therapeutic utility of free enzymes is impeded by their short circulation time, lack of targeting ability, immunogenicity, and inability to cross biological barriers. Cell-mediated drug delivery approach offers the unique capability to overcome these limitations, but the traditional cell-mediated enzyme delivery techniques suffer from drawbacks such as risk of intracellular degradation of and low loading capacity for the payload enzyme. This article presents the development of a novel cell-mediated enzyme delivery technique featuring the use of micrometer-sized disk-shaped particles termed microdevices. The microdevices are fabricated by layer-by-layer assembly and soft lithography with catalase being used as a model therapeutic enzyme. The amount of catalase in the microdevices can be controlled with the number of catalase layers. Catalase in the microdevices is catalytically active, and active catalase is slowly released from the microdevices. Moreover, cell-microdevice complexes are produced by attaching the catalase-laden microdevices to the external surface of both K562 cells and mouse embryonic stem cells. This technique is potentially applicable to other enzymes and cells and promises to be clinically useful.
酶已被用于治疗各种人类疾病和创伤。然而，游离酶的治疗用途受到其循环时间短、缺乏靶向能力、免疫原性以及无法穿越生物屏障等限制。细胞介导的药物输送方法具有克服这些限制的独特能力，但传统的细胞介导的酶输送技术存在一些缺点，如细胞内降解风险和对有效载荷酶的低装载能力。本文介绍了一种新型细胞介导的酶输送技术的发展，该技术的特点是使用微尺度盘状颗粒，称为微器件。微器件是通过层层组装和软光刻技术制造的，其中使用过氧化氢酶作为模型治疗酶。微器件中的过氧化氢酶的量可以通过过氧化氢酶层的数量来控制。微器件中的过氧化氢酶具有催化活性，并且活性过氧化氢酶从微器件中缓慢释放。此外，通过将载有过氧化氢酶的微器件附着在 K562 细胞和小鼠胚胎干细胞的外表面上，可以产生细胞-微器件复合物。该技术可能适用于其他酶和细胞，并有望在临床上有用。
