Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

By Martin P. Stewart, Robert Langer, Klavs F. Jensen. Chemical Reviews, 2018

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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 are important because they achieves rapid, direct, and universal delivery of almost any molecule that can be dispersed in solution. We start by covering the motivations for intracellular delivery and the challenges associated with the different cargo types – nucleic acids, proteins/peptides, small molecules, 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 the applications, challenges, and mechanisms of action. We hope the concepts discussed in our review inspire scientists and engineers with further ideas on how to improve intracellular delivery.

Subfields: Biomedical Engineering, Molecular Biology

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