Abstract

Ruthenium( II) coordination complexes have many appealing properties as prodrugs, but can suffer from poor aqueous solubility and short circulation times, drastically decreasing efficiency in vivo. Nanoformulations using a variety of carriers, such as inclusion in polymers/lipids or adsorption on inorganic nanoparticles have been applied to overcome this limitation, but unfortunately, these approaches raise additional concerns regarding the fate of the carriers, with potential long-term toxicity and accumulation in vital organs. Here, we present an alternative delivery strategy with formation of pure and polymer-supported supramolecular self-assemblies of Ru(II) complexes acting as ‘‘reservoirs’’. A facile preparation of size-controlled particles was achieved using a controlled precipitation method, and the approach was validate using [Ru(bpy)3](PF6)2 (bpy: 2,20-bipyridine) and [Ru(bpy)2(dmbpy)](PF6)2 (dmbpy: 6,60-dimethyl-2,20-bipyridine) as agents for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT). Negatively-charged particles ranging from tens of nanometers to micron scale were obtained by controlling just temperature and precipitation in the presence of confining polymers. Dissolution rate, biological activity, cellular uptake, and localization were evaluated in vitro in the dark or after light activation and revealed the progressive dissolution of the particles, associated with a gradual and sustained cellular uptake compared to the soluble molecule form. Leveraging the ability of the [Ru(bpy)3] to act as a 1 O2 photocatalyst for deposition of an osmiophilic polymer, electron microscopy was performed and illustrated the delivery of the dissolved complex inside the nucleus of cells. These results open new possibilities for the pure micro- or polymer-supported nano- formulation of Ru-based compounds, and provide a strategy for evaluation of subcellular localization using electron microscopy.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© The Royal Society of Chemistry 2026

Digital Object Identifier (DOI)

https://doi.org/10.1039/d5tb01785h

Funding Information

We gratefully acknowledge the support of the National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers R01GM138882 and R01GM107586 and the National Science Foundation (CHE-2333820).

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