Thioanisole ester based logic gate cascade to control ROS-triggered micellar degradation

Thioanisole ester based logic gate cascade to control ROS-triggered micellar degradation

Piergentili, I. (TU Delft ChemE/Advanced Soft Matter)
Bouwmans, Pepijn R. (Student TU Delft)
Reinalda, L. (TU Delft ChemE/Advanced Soft Matter)
Lewis, R.W. (TU Delft ChemE/Advanced Soft Matter)
Klemm, Benjamin (Student TU Delft)
Liu, H. (TU Delft RST/Applied Radiation & Isotopes)
de Kruijff, R.M. (TU Delft RST/Applied Radiation & Isotopes)
Denkova, A.G. (TU Delft RST/Applied Radiation & Isotopes)
Eelkema, R. (TU Delft ChemE/Advanced Soft Matter)

2022

In certain tumor and diseased tissues, reactive oxygen species (ROS), such as H₂O₂, are produced in higher concentrations than in healthy cells. Drug delivery and release systems that respond selectively to the presence of ROS, while maintaining their stability in “healthy” biological conditions, have great potential as on-site therapeutics. This study presents polymer micelles with 4-(methylthio)phenyl ester functionalities as a ROS-responsive reactivity switch. Oxidation of the thioether moieties triggers ester hydrolysis, exposing a hydrophylic carboxylate and leading to micellar disassembly. At 37 °C, the micelles fall apart on a timescale of days in the presence of 2 mM H₂O₂ and within hours at higher concentrations of H₂O₂ (60-600 mM). In the same time frame, the nanocarriers show no hydrolysis in oxidant-free physiological or mildly acidic conditions. This logic gate cascade behavior represents a step forward to realize drug delivery materials capable of selective response to a biomarker input.

http://resolver.tudelft.nl/uuid:19698a71-0d7f-40e8-900e-51247c455e7b

https://doi.org/10.1039/d2py00207h

1759-9954

Polymer Chemistry, 13, 2383-2390

Institutional Repository

journal article

© 2022 I. Piergentili, Pepijn R. Bouwmans, L. Reinalda, R.W. Lewis, Benjamin Klemm, H. Liu, R.M. de Kruijff, A.G. Denkova, R. Eelkema