Intracellular delivery is a key step in biological research and has enabled decades of biomedical discoveries. It is also becoming increasingly important in industrial and medical applications ranging from biomanufacture to cell-based therapies. Here, we review techniques for membrane disruption-based intracellular delivery from 1911 until the present. These methods achieve rapid, direct, and universal delivery of almost any cargo molecule or material that can be dispersed in solution. We start by covering the motivations for intracellular delivery and the challenges associated with the different cargo types—small molecules, proteins/peptides, nucleic acids, synthetic nanomaterials, and large cargo. The review then presents a broad comparison of delivery strategies followed by an analysis of membrane disruption mechanisms and the biology of the cell response. We cover mechanical, electrical, thermal, optical, and chemical strategies of membrane disruption with a particular emphasis on their applications and challenges to implementation. Throughout, we highlight specific mechanisms of membrane disruption and suggest areas in need of further experimentation. We hope the concepts discussed in our review inspire scientists and engineers with further ideas to improve intracellular delivery.

中文翻译：

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膜破坏的细胞内递送：机制、策略和概念

细胞内递送是生物学研究的关键步骤，并促成了数十年的生物医学发现。它在从生物制造到细胞疗法等工业和医疗应用中也变得越来越重要。在这里，我们回顾了从 1911 年至今基于膜破裂的细胞内递送技术。这些方法实现了几乎任何可分散在溶液中的货物分子或材料的快速、直接和普遍的递送。我们首先介绍细胞内递送的动机以及与不同货物类型（小分子、蛋白质/肽、核酸、合成纳米材料和大货物）相关的挑战。然后，该综述对递送策略进行了广泛的比较，随后分析了膜破坏机制和细胞反应的生物学。我们涵盖膜破坏的机械、电、热、光学和化学策略，特别强调它们的应用和实施挑战。在整个过程中，我们强调了膜破坏的具体机制，并提出了需要进一步实验的领域。我们希望我们的评论中讨论的概念能够激发科学家和工程师进一步的想法来改善细胞内递送。