Sankaran Shrikrishnan, Del Campo Aránzazu
INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.
Chemistry Department, Saarland University, 66123, Saarbrücken, Germany.
Adv Biosyst. 2019 Feb;3(2):e1800312. doi: 10.1002/adbi.201800312. Epub 2018 Dec 17.
Developing materials to encapsulate and deliver functional proteins inside the body is a challenging yet rewarding task for therapeutic purposes. High production costs, mostly associated with the purification process, short-term stability in vivo, and controlled and prolonged release are major hurdles for the clinical application of protein-based biopharmaceuticals. In an attempt to overcome these hurdles, herein, the possibility of incorporating bacteria as protein factories into a material and externally controlling protein release using optogenetics is demonstrated. By engineering bacteria to express and secrete a red fluorescent protein in response to low doses of blue light irradiation and embedding them in agarose hydrogels, living materials are fabricated capable of releasing proteins into the surrounding medium when exposed to light. These bacterial hydrogels allow spatially confined protein expression and dosed protein release over several weeks, regulated by the area and extent of light exposure. The possibility of incorporating such complex functions in a material using relatively simple material and genetic engineering strategies highlights the immense potential and versatility offered by living materials for protein-based biopharmaceutical delivery.
开发用于在体内封装和递送功能蛋白的材料，对于治疗目的而言是一项具有挑战性但又很有意义的任务。高生产成本（主要与纯化过程相关）、体内短期稳定性以及可控和长效释放，是基于蛋白质的生物药物临床应用的主要障碍。为了克服这些障碍，本文展示了将细菌作为蛋白质工厂整合到材料中，并使用光遗传学从外部控制蛋白质释放的可能性。通过对细菌进行工程改造，使其在低剂量蓝光照射下表达和分泌红色荧光蛋白，并将它们嵌入琼脂糖水凝胶中，制备出了活体材料，这种材料在受到光照时能够将蛋白质释放到周围介质中。这些细菌水凝胶能够在空间上限制蛋白质表达，并在数周内实现定量蛋白质释放，这可通过光照的面积和程度来调节。利用相对简单的材料和基因工程策略将此类复杂功能整合到材料中的可能性，凸显了活体材料在基于蛋白质的生物药物递送方面所具有的巨大潜力和多功能性。
