An Overview of Cell Membrane Perforation and Resealing Mechanisms for Localized Drug Delivery

doi:10.3390/pharmaceutics14040886

Review

. 2022 Apr 18;14(4):886.

doi: 10.3390/pharmaceutics14040886.

An Overview of Cell Membrane Perforation and Resealing Mechanisms for Localized Drug Delivery

Stephanie He¹, Davindra Singh¹, Brandon Helfield^{1

2}

Affiliations

¹ Department of Biology, Concordia University, Montreal, QC H4B 1R6, Canada.
² Department of Physics, Concordia University, Montreal, QC H4B 1R6, Canada.

PMID: 35456718
PMCID: PMC9031838
DOI: 10.3390/pharmaceutics14040886

Review

An Overview of Cell Membrane Perforation and Resealing Mechanisms for Localized Drug Delivery

Stephanie He et al. Pharmaceutics. 2022.

. 2022 Apr 18;14(4):886.

doi: 10.3390/pharmaceutics14040886.

Authors

Stephanie He¹, Davindra Singh¹, Brandon Helfield^{1

2}

Affiliations

¹ Department of Biology, Concordia University, Montreal, QC H4B 1R6, Canada.
² Department of Physics, Concordia University, Montreal, QC H4B 1R6, Canada.

PMID: 35456718
PMCID: PMC9031838
DOI: 10.3390/pharmaceutics14040886

Abstract

Localized and reversible plasma membrane disruption is a promising technique employed for the targeted deposition of exogenous therapeutic compounds for the treatment of disease. Indeed, the plasma membrane represents a significant barrier to successful delivery, and various physical methods using light, sound, and electrical energy have been developed to generate cell membrane perforations to circumvent this issue. To restore homeostasis and preserve viability, localized cellular repair mechanisms are subsequently triggered to initiate a rapid restoration of plasma membrane integrity. Here, we summarize the known emergency membrane repair responses, detailing the salient membrane sealing proteins as well as the underlying cytoskeletal remodeling that follows the physical induction of a localized plasma membrane pore, and we present an overview of potential modulation strategies that may improve targeted drug delivery approaches.

Keywords: cytoskeletal remodeling; endocytosis; exocytosis; membrane permeability; plasma membrane repair; pore; sonoporation; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Summary of known plasma membrane resealing mechanisms. (a) The tension–reduction hypothesis; (b) the patch hypothesis; (c) the ESCRT mechanism; and (d) exocytosis/endocytosis. See text for details.

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References

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[1] Allen T.M., Cullis P.R. Drug delivery systems: Entering the mainstream. Science. 2004;303:1818–1822. doi: 10.1126/science.1095833. - DOI - PubMed

[2] Allen T.M., Cullis P.R. Drug delivery systems: Entering the mainstream. Science. 2004;303:1818–1822. doi: 10.1126/science.1095833. - DOI - PubMed

[3] Manzari M.T., Shamay Y., Kiguchi H., Rosen N., Scaltriti M., Heller D.A. Targeted drug delivery strategies for precision medicines. Nat. Rev. Mater. 2021;6:351–370. doi: 10.1038/s41578-020-00269-6. - DOI - PMC - PubMed

[4] Manzari M.T., Shamay Y., Kiguchi H., Rosen N., Scaltriti M., Heller D.A. Targeted drug delivery strategies for precision medicines. Nat. Rev. Mater. 2021;6:351–370. doi: 10.1038/s41578-020-00269-6. - DOI - PMC - PubMed

[5] Stewart M.P., Langer R., Jensen K.F. Intracellular delivery by membrane disruption: Mechanisms, strategies, and concepts. Chem. Rev. 2018;118:7409–7531. doi: 10.1021/acs.chemrev.7b00678. - DOI - PMC - PubMed

[6] Stewart M.P., Langer R., Jensen K.F. Intracellular delivery by membrane disruption: Mechanisms, strategies, and concepts. Chem. Rev. 2018;118:7409–7531. doi: 10.1021/acs.chemrev.7b00678. - DOI - PMC - PubMed

[7] Peer D., Karp J.M., Hong S., FaroKhzad O.C., Margalit R., Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007;2:751–760. doi: 10.1038/nnano.2007.387. - DOI - PubMed

[8] Peer D., Karp J.M., Hong S., FaroKhzad O.C., Margalit R., Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007;2:751–760. doi: 10.1038/nnano.2007.387. - DOI - PubMed

[9] Langer R. New Methods of Drug Delivery. Science. 1990;249:1527–1533. doi: 10.1126/science.2218494. - DOI - PubMed

[10] Langer R. New Methods of Drug Delivery. Science. 1990;249:1527–1533. doi: 10.1126/science.2218494. - DOI - PubMed

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An Overview of Cell Membrane Perforation and Resealing Mechanisms for Localized Drug Delivery

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An Overview of Cell Membrane Perforation and Resealing Mechanisms for Localized Drug Delivery

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