Man Tiantian, Yu Guiling, Zhu Fulin, Huang Yaqi, Wang Yueyu, Su Yan, Deng Shengyuan, Pei Hao, Li Li, Ye Haifeng, Wan Ying
School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
JACS Au. 2024 Apr 6;4(4):1500-1508. doi: 10.1021/jacsau.4c00033. eCollection 2024 Apr 22.
Diabetes mellitus and its associated secondary complications have become a pressing global healthcare issue. The current integrated theranostic plan involves a glucometer-tandem pump. However, external condition-responsive insulin delivery systems utilizing rigid glucose sensors pose challenges in on-demand, long-term insulin administration. To overcome these challenges, we present a novel model of antidiabetic management based on printable metallo-nucleotide hydrogels and optogenetic engineering. The conductive hydrogels were self-assembled by bioorthogonal chemistry using oligonucleotides, carbon nanotubes, and glucose oxidase, enabling continuous glucose monitoring in a broad range (0.5-40 mM). The optogenetically engineered cells were enabled glucose regulation in type I diabetic mice via a far-red light-induced transgenic expression of insulin with a month-long avidity. Combining with a microchip-integrated microneedle patch, a prototyped close-loop system was constructed. The glucose levels detected by the sensor were received and converted by a wireless controller to modulate far-infrared light, thereby achieving on-demand insulin expression for several weeks. This study sheds new light on developing next-generation diagnostic and therapy systems for personalized and digitalized precision medicine.
糖尿病及其相关的继发性并发症已成为一个紧迫的全球医疗保健问题。当前的综合诊疗计划涉及血糖仪串联泵。然而,利用刚性葡萄糖传感器的外部条件响应胰岛素递送系统在按需长期胰岛素给药方面存在挑战。为了克服这些挑战,我们提出了一种基于可打印金属核苷酸水凝胶和光遗传学工程的新型抗糖尿病管理模型。导电水凝胶通过使用寡核苷酸、碳纳米管和葡萄糖氧化酶的生物正交化学自组装而成,能够在宽范围(0.5 - 40 mM)内连续监测葡萄糖。通过远红光诱导胰岛素的转基因表达,光遗传学工程细胞在I型糖尿病小鼠中实现了长达一个月的葡萄糖调节。结合微芯片集成微针贴片,构建了一个原型闭环系统。传感器检测到的葡萄糖水平由无线控制器接收并转换,以调节远红外光,从而实现数周的按需胰岛素表达。这项研究为开发用于个性化和数字化精准医学的下一代诊断和治疗系统提供了新的思路。