Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells

Ane Bretschneider Søgaard; Frederik Skovbo; Anne Tvilum; Rikke F. Hansson; Alexander N. Zelikin

doi:10.1002/adfm.202400048

Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells

Ane Bretschneider Søgaard, Frederik Skovbo, Anne Tvilum, Rikke F. Hansson, Alexander N. Zelikin^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

Receptors are lipid bilayer-resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non-genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell-specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody-drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody-drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor-engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio-orthogonal and thus afford a dedicated route of communication with the chemically engineered cells.

Original language	English
Article number	2400048
Journal	Advanced Functional Materials
Volume	34
Issue	33
Number of pages	9
ISSN	1616-301X
DOIs	https://doi.org/10.1002/adfm.202400048
Publication status	Published - Aug 2024

Keywords

antibody-drug conjugates
artificial receptors
chemical engineering of cells
drug targeting

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10.1002/adfm.202400048Licence: CC BY-NC-ND

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title = "Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells",

abstract = "Receptors are lipid bilayer-resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non-genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell-specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody-drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody-drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor-engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio-orthogonal and thus afford a dedicated route of communication with the chemically engineered cells.",

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Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells. / Søgaard, Ane Bretschneider ; Skovbo, Frederik; Tvilum, Anne et al.
In: Advanced Functional Materials, Vol. 34, No. 33, 2400048, 08.2024.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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T1 - Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells

AU - Søgaard, Ane Bretschneider

AU - Skovbo, Frederik

AU - Tvilum, Anne

AU - Hansson, Rikke F.

AU - Zelikin, Alexander N.

PY - 2024/8

Y1 - 2024/8

N2 - Receptors are lipid bilayer-resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non-genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell-specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody-drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody-drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor-engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio-orthogonal and thus afford a dedicated route of communication with the chemically engineered cells.

AB - Receptors are lipid bilayer-resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non-genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell-specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody-drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody-drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor-engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio-orthogonal and thus afford a dedicated route of communication with the chemically engineered cells.

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Artificial Internalizing Receptor Affords Fast, Potent, Specific Drug Delivery to the Chemically Engineered Cells

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