A multilayered cancer-on-a-chip model to analyze the effectiveness of new-generation photosensitizers
A multilayered cancer-on-a-chip model to analyze the effectiveness of new-generation photosensitizers
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DOI：
10.1039/d0an00911c
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发表时间：
2020-11-07
期刊：
影响因子：
4.2
通讯作者：
Brzozka, Zbigniew
中科院分区：
文献类型：
--
作者：
Flont, Magdalena;Jastrzebska, Elzbieta;Brzozka, Zbigniew
肿瘤组织的三维(3D)细胞模型是体外条件下分析新型抗癌药物的必要工具。卵巢癌的诊断和治疗是当前医学面临的主要挑战。在我们的报告中，我们提出了一种新的卵巢癌三维(3D)细胞模型，它可以模拟不同种类的癌症组织的片段。我们使用芯片实验室技术创建了一个微流控系统，允许培养细胞多层。细胞多层模拟了癌症组织的两个重要成分的结构：肉和间质。因此，它比其他体外细胞模型更具优势。我们在研究中使用了人卵巢成纤维细胞(HOF)和人卵巢癌细胞(A2780)。在研究的第一阶段，我们证明了与卵巢癌细胞共培养的非恶性成纤维细胞的存在刺激了癌细胞的增殖，这在卵巢癌的进展中起着重要的作用。在下一阶段的研究中，我们测试了新开发的细胞模型在体外条件下分析抗癌药物和治疗方法的有用性。我们测试了两种光敏剂(PS)：游离的和纳米包裹的Meso-四苯基卟啉，并评估了这些药物在卵巢癌的抗癌光动力疗法(PDT)中的潜力。通过对细胞培养中ROS水平的分析，对PDT的作用机制进行了初步探讨。我们的研究证实，使用新一代PS可以显着提高PDT治疗卵巢癌的疗效。我们还证明了新开发的3D细胞模型适合于抗癌药物的快速筛选，并有可能在未来的临床上使用，例如在抗癌个性化药物治疗方法的选择上。
Three-dimensional (3D) cellular models of cancer tissue are necessary tools to analyze new anticancer drugs under in vitro conditions. Diagnostics and treatment of ovarian cancer are major challenges for current medicine. In our report we propose a new three-dimensional (3D) cellular model of ovarian cancer which can mimic a fragment of heterogeneous cancer tissue. We used Lab-on-a-chip technology to create a microfluidic system that allows cellular multilayer to be cultured. Cellular multilayer mimics the structure of two important elements of cancer tissue: flesh and stroma. For this reason, it has an advantage over other in vitro cellular models. We used human ovarian fibroblasts (HOF) and human ovarian cancer cells in our research (A2780). In the first stage of the study, we proved that the presence of non-malignant fibroblasts in co-culture with ovarian cancer cells stimulates the proliferation of cancer cells, which is important in the progression of ovarian cancer. In the next stage of the research, we tested the usefulness of the newly-developed cellular model in the analysis of anticancer drugs and therapies under in vitro conditions. We tested two photosensitizers (PS): free and nanoencapsulated meso-tetrafenylporphyrin, and we evaluated the potential of these drugs in anticancer photodynamic therapy (PDT) of ovarian cancer. We also studied the mechanism of PDT based on the analysis of the level of reactive oxygen species (ROS) in cell cultures. Our research confirmed that the use of new-generation PS can significantly increase the efficacy of PDT in the treatment of ovarian cancer. We also proved that the newly-developed 3D cellular model is suitable for rapid screening of anticancer drugs and has the potential to be used clinically in the future, e.g. in the selection of treatment methods for anticancer personalized medicine.