化疗药物的临床应用受到几个因素的限制,包括低细胞摄取,循环时间短,和严重的不良影响。已提出细胞外囊泡(EV)作为具有克服这些限制的潜力的药物递送平台。电动汽车是细胞来源的,脂质双层纳米颗粒,对于细胞间通讯很重要。它们可以在全身运输生物活性货物,克服生物屏障,并靶向各种组织。几种小分子药物已成功纳入电动汽车的内腔,允许有效运输到肿瘤组织,增加治疗效力,减少不良影响。然而,货物装载往往不充分,精致的方法是成功利用平台的先决条件。通过系统地评估改变负荷参数对电穿孔的影响,例如电动汽车的总数,药物与EV的比率,缓冲区,脉冲电容,和场强,我们能够区分趋势和相关性。这使我们能够设计一种优化的电穿孔方案,用于将化疗药物阿霉素加载到EV中。装载技术证明了货物装载和电动汽车回收的改善,以及药物效力,与裸阿霉素相比,反应增加了190倍。
The clinical use of chemotherapeutics is limited by several factors, including low cellular uptake, short circulation time, and severe adverse effects. Extracellular vesicles (EVs) have been suggested as a drug delivery platform with the potential to overcome these limitations. EVs are cell-derived, lipid bilayer nanoparticles, important for intercellular communication. They can transport bioactive cargo throughout the body, surmount biological barriers, and target a variety of tissues. Several small molecule drugs have been successfully incorporated into the lumen of EVs, permitting efficient transport to tumour tissue, increasing therapeutic potency, and reducing adverse effects. However, the cargo loading is often inadequate and refined methods are a prerequisite for successful utilisation of the platform. By systematically evaluating the effect of altered loading parameters for electroporation, such as total number of EVs, drug to EV ratio, buffers, pulse capacitance, and field strength, we were able to distinguish tendencies and correlations. This allowed us to design an optimised electroporation protocol for loading EVs with the chemotherapeutic drug doxorubicin. The loading technique demonstrated improved cargo loading and EV recovery, as well as drug potency, with a 190-fold increased response compared to naked doxorubicin.