TY - JOUR
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.
KW - antibody-drug conjugates
KW - artificial receptors
KW - chemical engineering of cells
KW - drug targeting
UR - http://www.scopus.com/inward/record.url?scp=85189086016&partnerID=8YFLogxK
U2 - 10.1002/adfm.202400048
DO - 10.1002/adfm.202400048
M3 - Journal article
AN - SCOPUS:85189086016
SN - 1616-301X
VL - 34
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 33
M1 - 2400048
ER -