Sophorolipids are biosurfactants derived from the non-pathogenic yeast Starmerella bombicola, with potential efficacy in anti-cancer applications. Simple and cost-effective synthesis of these drugs makes them a promising alternative to traditional chemotherapeutics, pending their success in preliminary drugscreening. Drug screening typically utilizes 2D cell monolayers due to their simplicity and potential for high-throughput assessment. However, 2D assays fail to capture the complexity and 3D context of the tumor microenvironment, and have consequently been implicated in the high percentage of drugs investigated in vitro that later fail in clinical trials. We screened two sophorolipid candidates and clinically-used chemotherapeutic, doxorubicin, on in vitro breast cancer models ranging from 2D monolayers to 3D spheroids, employing Optical Coherence Tomography to confirm these morphologies. We calculated corresponding IC₅₀ values for these drugs and found one of the sophorolipids to have comparable toxicities to the chemotherapeutic control. Our findings show increased drug resistance associated with model dimensionality, such that all drugs tested showed that 3D spheroids exhibited higher IC₅₀ values than their 2D counterparts. These findings demonstrate promising preliminary data to support the use of sophorolipids as a more affordable alternative to traditional clinical interventions and demonstrate the importance of 3D tumor models in assessing drug response.

中文翻译：

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槐糖脂候选者展示了对 2D 和 3D 乳腺癌模型的细胞毒性功效

槐糖脂是源自非致病性酵母Starmerella bombicola的生物表面活性剂，在抗癌应用中具有潜在功效。这些药物的简单且具有成本效益的合成使它们成为传统化学疗法的有希望的替代品，等待它们在初步药物筛选中的成功。由于其简单性和高通量评估的潜力，药物筛选通常使用 2D 细胞单层。然而，2D 分析无法捕捉肿瘤微环境的复杂性和 3D 背景，因此与后来在临床试验中失败的体外研究药物的高比例有关。我们在体外筛选了两种槐糖脂候选物和临床使用的化疗药物阿霉素乳腺癌模型从 2D 单层到 3D 球体，采用光学相干断层扫描来确认这些形态。我们计算了这些药物的相应IC ₅₀值，并发现其中一种槐糖脂具有与化疗对照相当的毒性。我们的研究结果表明与模型维度相关的耐药性增加，因此所有测试的药物都表明 3D 球体表现出比 2D 对应物更高的 IC _50值。这些发现证明了有希望的初步数据支持使用槐糖脂作为传统临床干预的更实惠的替代品，并证明 3D 肿瘤模型在评估药物反应中的重要性。