Jarvis Maria, Arnold Michael, Ott Jenna, Pant Kapil, Prabhakarpandian Balabhaskar, Mitragotri Samir
Biomolecular Sciences and Engineering Program University of California Santa Barbara CA 93106.
Dept. of Molecular, Cellular and Developmental Biology University of California Santa Barbara CA 93106.
Bioeng Transl Med. 2017 Sep 26;2(3):268-277. doi: 10.1002/btm2.10079. eCollection 2017 Sep.
In vitro and in vivo assessment of safety and efficacy are the essential first steps in developing nanoparticle-based therapeutic systems. However, it is often challenging to use the knowledge gained from in vitro studies to predict the outcome of in vivo studies since the complexity of the in vivo environment, including the existence of flow and a multicellular environment, is often lacking in traditional in vitro models. Here, we describe a microfluidic co-culture model comprising 4T1 breast cancer cells and EA.hy926 endothelial cells under physiological flow conditions and its utilization to assess the penetration of therapeutic nanoparticles from the vascular compartment into a cancerous cell mass. Camptothecin nanocrystals (∼310 nm in length), surface-functionalized with PEG or folic acid, were used as a test nanocarrier. Camptothecin nanocrystals exhibited only superficial penetration into the cancerous cell mass under fluidic conditions, but exhibited cytotoxicity throughout the cancerous cell mass. This likely suggests that superficially penetrated nanocrystals dissolve at the periphery and lead to diffusion of molecular camptothecin deep into the cancerous cell mass. The results indicate the potential of microfluidic co-culture devices to assess nanoparticle-cancerous cell interactions, which are otherwise difficult to study using standard in vitro cultures.
对基于纳米颗粒的治疗系统进行体外和体内的安全性和有效性评估是开发过程中必不可少的首要步骤。然而，利用体外研究获得的知识来预测体内研究的结果往往具有挑战性，因为体内环境的复杂性，包括流动的存在和多细胞环境，在传统的体外模型中常常缺失。在此，我们描述了一种微流控共培养模型，该模型在生理流动条件下包含4T1乳腺癌细胞和EA.hy926内皮细胞，并利用其评估治疗性纳米颗粒从血管腔进入癌细胞团的渗透情况。用聚乙二醇（PEG）或叶酸进行表面功能化的喜树碱纳米晶体（长度约为310 nm）被用作测试纳米载体。在流体条件下，喜树碱纳米晶体仅能浅层渗透到癌细胞团中，但在整个癌细胞团中均表现出细胞毒性。这可能表明，浅层渗透的纳米晶体在周边溶解，导致分子喜树碱扩散到癌细胞团深部。结果表明微流控共培养装置在评估纳米颗粒与癌细胞相互作用方面的潜力，而这在标准体外培养中很难进行研究。
