Multimodal Strategies for Resuscitating Injured Cells

Agarwal, Jayant P.; Walsh, Alexandra; Lee, Raphael C.

doi:10.1196/annals.1363.027

Cited by 13 publications

(14 citation statements)

References 68 publications

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“…The concept of optimizing intracellular delivery by manipulating cell response has received sporadic attention over the past decades. As mentioned above, some positive results have been reported from supplementation with membrane healing polymers 178,420–425 and antioxidants 421,426,427,428 . Most of the work to date, however, has focused on engineering the permeabilization buffer.…”

Section: Membrane Disruption-mediated Delivery: Background Conceptsmentioning

confidence: 87%

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

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 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.

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Section: Membrane Disruption-mediated Delivery: Background Conceptsmentioning

confidence: 87%

“…A third possibility is that collision of detergent micelles with the cell membranes recruits lipids units into the micelles, thereby generating defects in the membrane (Figure 34) 421,1336 . There is little theory to support this third possibility, however it should be mentioned as a possibility.…”

Section: Intracellular Delivery By Permeabilizationmentioning

confidence: 99%

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

2018

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“…While this allows a wide range of submicron particulate matter to be delivered into the cell, a downside of a large proportion of these methods, however, lies in the damage inflicted on the cells during the poration process. 4 Electroporation, for example, which necessitates the application of high electric potentials across the cell membrane, often results in irreversible damage to the cell membrane, leading to a loss in homeostasis in the cell 5,6 and eventually apoptosis. [7][8][9] Sonoporation, on the other hand, primarily exploits the cavitation of microbubbles induced by sound waves near the cell membrane to enhance its permeabilisation.…”

Section: Introductionmentioning

confidence: 99%

Acoustically-mediated intracellular delivery

et al. 2018

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Recent breakthroughs in gene editing have necessitated practical ex vivo methods to rapidly and efficiently re-engineer patient-harvested cells. Many physical membrane-disruption or pore-forming techniques for intracellular delivery, however, result in poor cell viability, while most carrier-mediated techniques suffer from suboptimal endosomal escape and hence cytoplasmic or nuclear targeting. In this work, we show that short exposure of cells to high frequency (>10 MHz) acoustic excitation facilitates temporal reorganisation of the lipid structure in the cell membrane that enhances translocation of gold nanoparticles and therapeutic molecules into the cell within just ten minutes. Due to its transient nature, rapid cell self-healing is observed, leading to high cellular viabilities (>97%). Moreover, the internalised cargo appears to be uniformly distributed throughout the cytosol, circumventing the need for strategies to facilitate endosomal escape. In the case of siRNA delivery, the method is seen to enhance gene silencing by over twofold, demonstrating its potential for enhancing therapeutic delivery into cells.

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“…The cell membrane is a permselective barrier that controls the material transport and energy exchange between extra- and intracellular fluids. , As a relatively vulnerable interface, many types of injury can disrupt the cell membrane structure, including thermal trauma, frostbite, electric shock, , radical-mediated radiation, and barometric trauma. , Therapeutically, membrane integrity can be restored by surfactants that interact with the lipid bilayers . Pluronics, also known as poloxamers, are one widely used surfactant family.…”

Section: Introductionmentioning

confidence: 99%

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers

et al. 2017

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Block copolymers composed of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) have been widely used in cell membrane stabilization and permeabilization. To explore the mechanism of interaction between PPO-PEO block copolymers and lipid membranes, we have investigated how polymer structure influences the polymer-lipid bilayer association by varying the overall molecular weight, the hydrophobic and hydrophilic block lengths, and the endgroup structure systematically, using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) unilamellar liposomes as model membranes. Pulsed-field-gradient NMR (PFG-NMR) was employed to probe polymer diffusion in the absence and presence of liposomes. The echo decay curves of free polymers in the absence of liposomes are single exponentials, indicative of simple translational diffusion, while in the presence of liposomes, the decays were biexponential, with the slower decay corresponding to polymers bound to liposomes. The binding percentage of polymer to the liposome was quantified by fitting the echo decay curves to a biexponential model. The NMR experiments showed that increasing the total molecular weight and hydrophobicity of the polymer can significantly enhance the polymer-lipid bilayer association, as the binding percentage and liposome surface coverage both increase. We hypothesize that the hydrophobic PPO block inserts into the lipid bilayer, due to the fact that little molecular exchange between bound and free polymers occurs on the time scale of the diffusion experiments. Additionally, as polymer concentration increases, the liposome surface coverage increases and approaches a limit. These results demonstrate that PFG-NMR is a simple yet powerful method to quantify interactions between polymers and lipid bilayers.

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Multimodal Strategies for Resuscitating Injured Cells

Cited by 13 publications

References 68 publications

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

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

Acoustically-mediated intracellular delivery

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers

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