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Polymer encapsulation of ruthenium complexes for biological and medicinal applications

Abstract

Some Ru complexes have extremely promising anticancer or antibacterial properties, but the poor H2O solubility and/or low stability of many Ru complexes in aqueous solution under physiological conditions and/or metabolic or biodistribution profiles prevent their therapeutic use. To overcome these drawbacks, various strategies have been developed to improve the delivery of these compounds to their target tissues. The first strategy is based on physical encapsulation of Ru complexes in carriers, such as polymeric micelles, microparticles, nanoparticles and polymer–lipid hybrids, which enables the delivery and controlled release of the active Ru drug candidate. The second strategy involves covalent conjugation of the Ru complex to a polymer to give a prodrug that can be converted into the active drug at a more controllable rate. In this Review, we provide an overview of recent developments in polymer encapsulation of Ru complexes for biological and medicinal applications. We place particular emphasis on how polymer structure affects Ru delivery.

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Fig. 1: Representative Ru complexes with medicinal potential.
Fig. 2: Methods to encapsulate Ru complexes in polymers.
Fig. 3: Some prominent biodegradable polymers.
Fig. 4: Synthetic strategies for Ru-conjugated polymer prodrug candidates.
Fig. 5: Photoactivatable nanocarriers.
Fig. 6: Ru–polymer conjugates can be activated either by biodegradation or light.
Fig. 7: Synthesis of Ru complexes bearing ligands with 2–6 polymer chains.

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Acknowledgements

The authors acknowledge funding from École Nationale Supérieure de Chimie de Paris (ENSCP), the Centre National de la Recherche Scientifique (CNRS), a European Research Council (ERC) Consolidator Grant PhotoMedMet GA 681679 (G.G.), the Swiss National Science Foundation Grant Sinergia CRSII5_173718 (G.G.) and the Investissements d’Avenir programme launched by the French government and implemented by the Agence Nationale de la Recherche (ANR), reference ANR-10-IDEX-0001-02 PSL (G.G.). C.M.T. thanks the Institut Universitaire de France (IUF) for financial support.

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Villemin, E., Ong, Y.C., Thomas, C.M. et al. Polymer encapsulation of ruthenium complexes for biological and medicinal applications. Nat Rev Chem 3, 261–282 (2019). https://doi.org/10.1038/s41570-019-0088-0

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