Simultaneous activation and release of a microtubule inhibitor from amphiphilic polymeric nanoparticles
- 1aDepartment of Chemical Engineering & Chemistry and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
- 2bThe Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Abstract
Light addressable drug delivery systems offer opportunities to achieve spatiotemporal control over therapeutic activity while minimising off-target effects. Here we report the design, synthesis, and evaluation of a photocaged photostatin (proPST-1), in which the phenolic group of photostatin-1 (PST-1) was masked with an o-nitrobenzyl (ONB) photocage. Our strategy combines reversible photoswitching of the azobenzene unit with irreversible photolysis of the ONB group, affording active PST-1. Molecular docking studies suggested reduced predicted tubulin compatibility of proPST-1 due to the bulky ONB group relative to PST-1 thus silencing the dark state activity and enabling optical ON-switching. Encapsulation of proPST-1 within polymeric nanoparticles (PNs) formed from an amphiphilic polymer resulted in water soluble nanocarriers with high encapsulation efficiencies of proPST-1 (∼95%). Upon 365 nm irradiation, photolysis released the active cis-PST-1, weakening hydrophobic partitioning and promoting release from the nanoparticle core. In vitro tubulin polymerisation assays confirmed pronounced light-dependent inhibition, while cytotoxicity assays in cells validated concentration-dependent activity only after irradiation. This proof-of-concept study establishes a blueprint for integrating photocaging and photoswitching within nanocarriers to achieve dual activation and triggered release.
Related
- Oil Recovery by Synergistic CO2 Flooding Using Viscoelastic Fluids of Low Interfacial Tension Containing Amphiphilic Nanoparticles
- Theranostic silica nanoparticles for selective and simultaneous delivery of paclitaxel and coumarin to hypoxic tumors
- Dual-Responsive Nanoparticles for Prodrug Activation and Copper-Dependent Cell Death
- Electroacoustic activation of natural quartz nanoparticles for the Guareschi–Thorpe synthesis of novel pyridine derivatives
- Synthesis of Amphiphilic Polymer Co-Networks via the Growth of a Living RAFT Network. Part II: PEGDA-Based Parent Networks
BibTeX
@article{singh2026simultaneous,
title = {{Simultaneous activation and release of a microtubule inhibitor from amphiphilic polymeric nanoparticles}},
author = {Harshit Singh and Anand Kumar Thotakura and A. P. Prakasham and Esmee de Korver and Anja R. A. Palmans},
journal = {Nanoscale advances},
year = {2026},
month = oct,
doi = {10.1039/d6na00763e},
url = {https://europepmc.org/article/PMC/PMC13673699},
note = {CC BY},
}
RIS
TY - JOUR
TI - Simultaneous activation and release of a microtubule inhibitor from amphiphilic polymeric nanoparticles
AU - Harshit Singh
AU - Anand Kumar Thotakura
AU - A. P. Prakasham
AU - Esmee de Korver
AU - Anja R. A. Palmans
PY - 2026
DA - 2026/10/01
JO - Nanoscale advances
DO - 10.1039/d6na00763e
UR - https://europepmc.org/article/PMC/PMC13673699
AB - Light addressable drug delivery systems offer opportunities to achieve spatiotemporal control over therapeutic activity while minimising off-target effects. Here we report the design, synthesis, and evaluation of a photocaged photostatin (proPST-1), in which the phenolic group of photostatin-1 (PST-1) was masked with an o-nitrobenzyl (ONB) photocage. Our strategy combines reversible photoswitching of the azobenzene unit with irreversible photolysis of the ONB group, affording active PST-1. Molecular docking studies suggested reduced predicted tubulin compatibility of proPST-1 due to the bulky ONB group relative to PST-1 thus silencing the dark state activity and enabling optical ON-switching. Encapsulation of proPST-1 within polymeric nanoparticles (PNs) formed from an amphiphilic polymer resulted in water soluble nanocarriers with high encapsulation efficiencies of proPST-1 (∼95%). Upon 365 nm irradiation, photolysis released the active cis-PST-1, weakening hydrophobic partitioning and promoting release from the nanoparticle core. In vitro tubulin polymerisation assays confirmed pronounced light-dependent inhibition, while cytotoxicity assays in cells validated concentration-dependent activity only after irradiation. This proof-of-concept study establishes a blueprint for integrating photocaging and photoswitching within nanocarriers to achieve dual activation and triggered release.
SN - 2516-0230
ER -