The most challenging phase in the clinical translation of drugs is the complex process of screening various drugs and evaluating their therapeutic effects in vitro and in vivo. Microfluidic models have been recognized as an interesting alternative to animal models for drug screening. Enhanced permeation and retention (EPR) effect is one of the most widely used standard for drug delivery in solid tumors with high vascular density and active angiogenesis. The nascent blood vessels in the tumor vicinity have large gaps between the endothelial junctions which allow nanoparticles to pass through them, resulting in selective extravasation and passive accumulation in the tumor regions. In this study, an attempt has been made to mimic some of the physiological characteristics in solid tumors such as endothelial gap junctions, obstructed blood vessels and EPR using a microfluidic platform for drug screening under dynamic culture conditions. The microfluidic chip was fabricated using soft lithography technique. Numerical simulations were performed to analyze the flow patterns inside the chip. Fluorescent gold nanoclusters (Au NCs) were synthesized and their accumulation in the tumor cells cultured inside the microfluidic chip was studied. The experimental results showed an increased uptake of Au NCs in the cells near the endothelial gap junctions in comparison to the cells away from the junctions. The observations in the study correlated with the leaky nature of the tumor vasculature, owing to the enhancement of vascularization and thereby EPR effect. Hence, the fabricated microfluidic device has the potential of minimizing the number of pre-clinical trials using animal models, allowing easier drug screening.

药物临床翻译中最具挑战性的阶段是筛选各种药物并评估其体外和体内治疗效果的复杂过程。微流体模型已被认为是用于药物筛选的动物模型的一种有趣替代方法。增强的渗透和保留（EPR）效应是在具有高血管密度和活跃血管生成的实体瘤中最广泛使用的药物递送标准之一。肿瘤附近的新生血管在内皮连接处之间有较大的间隙，使纳米颗粒可以通过它们，从而导致肿瘤区域中的选择性外渗和被动积累。在这项研究中，我们尝试模仿实体瘤中的某些生理特征，例如内皮间隙连接，在动态培养条件下，使用微流控平台对血管和EPR进行阻塞，以进行药物筛选。使用软光刻技术制造微流体芯片。进行数值模拟以分析芯片内部的流动模式。合成了荧光金纳米簇（Au NCs），并研究了它们在微流控芯片内部培养的肿瘤细胞中的积累。实验结果表明，与远离间隙连接的细胞相比，内皮间隙连接附近的细胞对Au NCs的吸收增加。由于血管形成的增强以及EPR的作用，该研究中的观察结果与肿瘤脉管系统的渗漏性有关。因此，