体外,药物评估在新药开发和精准医学方面具有巨大的成功潜力。传统的药物评估技术,然而,面临着实现高速的巨大挑战,受基于孵育的药物递送(>几个小时)和细胞活力测量(>1天)的限制,这在临床试验中显著降低了疗效。在这项工作中,据报道,纳米电穿孔-DNA张紧器平台可将药物输送时间缩短至小于3s,和细胞机械力分析到30分钟。该平台采用纳米通道结构,可定位细胞穿孔的安全电场,同时将细胞内递送的递送速度提高103倍,与共培养方法中的分子扩散相比。平台还配备有DNA张紧器以检测细胞机械力,用于定量药物处理后的细胞活力。系统的头对头比较,通过分析FDA(食品和药物管理局)批准的药物(紫杉醇,阿霉素),展示了高速的平台,效率,和安全,显示临床药物筛选和开发的简单而强大的工具。
In vitro, drug assessment holds tremendous potential to success in novel drug development and precision medicine. Traditional techniques for drug assessment, however, face remarkable challenges to achieve high speed, as limited by incubation-based drug delivery (>several hours) and cell viability measurements (>1 d), which significantly compromise the efficacy in clinical trials. In this work, a nano-electroporation-DNA tensioner platform is reported that shortens the time of drug delivery to less than 3 s, and that of cellular mechanical force analysis to 30 min. The platform adopts a nanochannel structure to localize a safe electric field for cell perforation, while enhancing delivery speed by 103 times for intracellular delivery, as compared to molecular diffusion in coculture methods. The platform is further equipped with a DNA tensioner to detect cellular mechanical force for quantifying cell viability after drug treatment. Systematic head-to-head comparison, by analyzing FDA (food and drug administration)-approved drugs (paclitaxel, doxorubicin), demonstrated the platform with high speed, efficiency, and safety, showing a simple yet powerful tool for clinical drug screening and development.