PDF(Pubmed)
Abstract：
Bacteria-assisted chemotherapeutics have been highlighted as an alternative or supplementary approach to treating cancer. However, dynamic cancer-microbe studies at the in vitro level have remained a challenge to show the impact and effectiveness of microbial therapeutics due to the lack of relevant coculture models. Here, we demonstrate a hydrogel-based compartmentalized system for prodrug activation of a natural ingredient of licorice root, glycyrrhizin, by microbial β-glucuronidase (GUS). Hydrogel containment with Lactococcus lactis provides a favorable niche to encode GUS enzymes with excellent permeability and can serve as an independent ecosystem in the transformation of pro-apoptotic materials. Based on the confinement system of GUS expressing microbes, we quantitatively evaluated chemotherapeutic effects enhanced by microbial GUS enzyme in two dynamic coculture models in vitro (i.e., 2D monolayered cancer cells and 3D tumor spheroids). Our findings support the processes of prodrug conversion mediated by bacterial GUS enzyme which can enhance the therapeutic efficacy of a chemotherapy drug under dynamic coculture conditions. We expect our in vitro coculture platforms can be used for the evaluation of pharmacological properties and biological activity of xenobiotics as well as the potential impact of microbes on cancer therapeutics.
摘要：
细菌辅助化学疗法已被强调为治疗癌症的替代或补充方法。然而,由于缺乏相关的共培养模型,体外水平的动态癌症-微生物研究对于显示微生物疗法的影响和有效性仍然是一个挑战.这里,我们展示了一种基于水凝胶的分隔系统，用于前药激活甘草根的天然成分，甘草酸，通过微生物β-葡糖醛酸酶（GUS）。具有乳酸乳球菌的水凝胶容纳为编码具有优异渗透性的GUS酶提供了有利的生态位，并且可以在促凋亡物质的转化中充当独立的生态系统。基于GUS表达微生物的禁闭系统，我们在两个体外动态共培养模型中定量评估了微生物GUS酶增强的化疗效果(即，2D单层癌细胞和3D肿瘤球体）。我们的发现支持了由细菌GUS酶介导的前药转化过程，该过程可以在动态共培养条件下增强化疗药物的疗效。我们希望我们的体外共培养平台可用于评估外源性物质的药理特性和生物活性以及微生物对癌症治疗的潜在影响。
