Issue 22, 2022, Issue in Progress

Tuning the affinity of amphiphilic guest molecules in a supramolecular polymer transient network

Abstract

Dynamicity plays a central role in biological systems such as in the cellular microenvironment. Here, the affinity and dynamics of different guest molecules in a transient supramolecular polymer hydrogel system, i.e. the host network, are investigated. The hydrogel system consists of bifunctional ureido-pyrimidinone (UPy) poly(ethylene glycol) polymers. A monofunctional complementary UPy guest is introduced, designed to interact with the host network based on UPy–UPy interactions. Furthermore, two other guest molecules are synthesized, being cholesterol and dodecyl (c12) guests; both designed to interact with the host network via hydrophobic interactions. At the nanoscale in solution, differences in morphology of the guest molecules were observed. The UPy–guest molecule formed fibers, and the cholesterol and c12 guests formed aggregates. Furthermore, cellular internalization of fluorescent guest molecules was studied. No cellular uptake of the UPy–cy5 guest was observed, whereas the cholesterol–cy5 guest showed membrane binding and cellular uptake. Also the c12–cy5 guest showed cellular uptake. Formulation of the guest molecules into the UPy hydrogel system was done to study the guest–host affinity. No changes in mechanical properties as measured with rheology were found upon guest–hydrogel formulation. Fluorescence recovery after photobleaching showed the diffusive properties of the cy5-functionalized guests throughout the host network. The c12 guest displayed a relatively fast mobility, the UPy guest displayed a decrease in mobility, and the cholesterol–guest remained relatively stable in the host network with little mobility. This demonstrates the tunable dynamic differences of affinity-based interaction between guest molecules and the host network. Interestingly, the cholesterol guest is internalized in cells and is robustly incorporated in the hydrogel network, while the UPy guest is not taken up by cells but shows an affinity to the hydrogel network. These results show the importance of guest–hydrogel affinity for future drug release. However, if modified with cholesterol these guests, or future drugs, will be taken up by cells; if modified with a UPy unit this does not occur. In this way both the drug–hydrogel interaction and the cell internalization behavior can be tuned. Regulating the host–guest dynamics in transient hydrogels opens the door to various drug delivery purposes and tissue engineering.

Graphical abstract: Tuning the affinity of amphiphilic guest molecules in a supramolecular polymer transient network

Article information

Article type
Paper
Submitted
17 1 2022
Accepted
11 4 2022
First published
10 5 2022
This article is Open Access
Creative Commons BY license

RSC Adv., 2022,12, 14052-14060

Tuning the affinity of amphiphilic guest molecules in a supramolecular polymer transient network

M. J. G. Schotman, P. Fransen, J. Song and P. Y. W. Dankers, RSC Adv., 2022, 12, 14052 DOI: 10.1039/D2RA00346E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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