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Catalytically Active Single-Chain Polymeric Nanoparticles: Exploring Their Functions in Complex Biological Media
journal contribution
posted on 2018-02-19, 00:00 authored by Yiliu Liu, Sílvia Pujals, Patrick J. M. Stals, Thomas Paulöhrl, Stanislav I. Presolski, E. W. Meijer, Lorenzo Albertazzi, Anja R. A. PalmansDynamic single-chain polymeric nanoparticles
(SCPNs) are intriguing,
bioinspired architectures that result from the collapse or folding
of an individual polymer chain into a nanometer-sized particle. Here
we present a detailed biophysical study on the behavior of dynamic
SCPNs in living cells and an evaluation of their catalytic functionality
in such a complex medium. We first developed a number of delivery
strategies that allowed the selective localization of SCPNs in different
cellular compartments. Live/dead tests showed that the SCPNs were
not toxic to cells while spectral imaging revealed that SCPNs provide
a structural shielding and reduced the influence from the outer biological
media. The ability of SCPNs to act as catalysts in biological media
was first assessed by investigating their potential for reactive oxygen
species generation. With porphyrins covalently attached to the SCPNs,
singlet oxygen was generated upon irradiation with light, inducing
spatially controlled cell death. In addition, Cu(I)- and Pd(II)-based
SCPNs were prepared and these catalysts were screened in vitro and studied in cellular environments for the carbamate cleavage
reaction of rhodamine-based substrates. This is a model reaction for
the uncaging of bioactive compounds such as cytotoxic drugs for catalysis-based
cancer therapy. We observed that the rate of the deprotection depends
on both the organometallic catalysts and the nature of the protective
group. The rate reduces from in vitro to the biological
environment, indicating a strong influence of biomolecules on catalyst
performance. The Cu(I)-based SCPNs in combination with the dimethylpropargyloxycarbonyl
protective group showed the best performances both in vitro and in biological environment, making this group promising in biomedical
applications.
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bioinspired architecturesorganometallic catalystsSingle-Chain Polymeric Nanoparticlesreactive oxygen species generationdelivery strategiescytotoxic drugsnanometer-sized particleMedia Dynamic single-chaincatalysis-based cancer therapycatalyst performancerhodamine-based substratessinglet oxygenporphyrins covalentlymodel reactionbioactive compoundspolymer chaincarbamate cleavage reactioncell deathSCPN
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