Anticancer drug development is a crucial step toward cancer treatment, that requires realistic predictions of malignant tissue development and sophisticated drug delivery. Tumors often acquire drug resistance and drug efficacy, hence cannot be accurately predicted in 2D tumor cell cultures. On the other hand, 3D cultures, including multicellular tumor spheroids (MCTSs), mimic the in vivo cellular arrangement and provide robust platforms for drug testing when grown in hydrogels with characteristics similar to the living body. Microparticles and liposomes are considered smart drug delivery vehicles, are able to target cancerous tissue, and can release entrapped drugs on demand. Microfluidics serve as a high-throughput tool for reproducible, flexible, and automated production of droplet-based microscale constructs, tailored to the desired final application. In this review, it is described how natural hydrogels in combination with droplet microfluidics can generate MCTSs, and the use of microfluidics to produce tumor targeting microparticles and liposomes. One of the highlights of the review documents the use of the bottom-up construction methodologies of synthetic biology for the formation of artificial cellular assemblies, which may additionally incorporate both target cancer cells and prospective drug candidates, as an integrated “droplet incubator” drug assay platform.

中文翻译：

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用于肿瘤药物相关研究和可编程人造细胞的液滴微流体

抗癌药物的开发是癌症治疗的关键一步，这需要对恶性组织的发展和复杂的药物输送进行现实的预测。肿瘤通常会产生耐药性和药物疗效，因此无法在二维肿瘤细胞培养中准确预测。另一方面，包括多细胞肿瘤球体 (MCTS) 在内的 3D 培养物可模拟体内细胞排列，并在具有与活体相似特性的水凝胶中生长时，为药物测试提供强大的平台。微粒和脂质体被认为是智能药物输送载体，能够靶向癌组织，并可以根据需要释放包埋的药物。微流体作为一种高通量工具，可重复、灵活和自动化地生产基于液滴的微尺度结构，并根据所需的最终应用进行定制。在这篇综述中，描述了天然水凝胶如何与液滴微流体相结合产生MCTS，以及使用微流体来生产肿瘤靶向微粒和脂质体。该评论的亮点之一记录了使用合成生物学自下而上的构建方法来形成人工细胞组件，该组件还可以包含靶癌细胞和潜在候选药物，作为集成的“液滴孵化器”药物测定平台。