Bioluminescence Resonance Energy Transfer (BRET)-Mediated Protein Release from Self-Illuminating Photoresponsive Biomaterials.

Phototriggered release of various cargos, including soluble protein factors and small molecules, has the potential to correct aberrant biological events by offering spatiotemporal control over local therapeutic levels. However, the poor penetration depth of light historically limits implementation to subdermal regions, necessitating alternative methods of light delivery to achieve the full potential of photodynamic therapeutic release. Here, we introduce a strategy exploiting bioluminescence resonance energy transfer (BRET)-an energy transfer process between light-emitting Nanoluciferase (NLuc) and a photosensitive acceptor molecule-to drive biomolecule release from hydrogel biomaterials.

Tricolor visible wavelength-selective photodegradable hydrogel biomaterials.

Photodynamic hydrogel biomaterials have demonstrated great potential for user-triggered therapeutic release, patterned organoid development, and four-dimensional control over advanced cell fates in vitro. Current photosensitive materials are constrained by their reliance on high-energy ultraviolet light (<400 nm) that offers poor tissue penetrance and limits access to the broader visible spectrum. Here, we report a family of three photolabile material crosslinkers that respond rapidly and with unique tricolor wavelength-selectivity to low-energy visible light (400-617 nm).

Targeting drug delivery with light: A highly focused approach.

Light is a uniquely powerful tool for controlling molecular events in biology. No other external input (e.g.

Visible Light-Responsive Dynamic Biomaterials: Going Deeper and Triggering More.

Photoresponsive materials have been widely used in vitro for controlled therapeutic delivery and to direct 4D cell fate. Extension of the approaches into a bodily setting requires use of low-energy, long-wavelength light that penetrates deeper into and through complex tissue. This review details recent reports of photoactive small molecules and proteins that absorb visible and/or near-infrared light, opening the door to exciting new applications in multiplexed and in vivo regulation.

Designing Photolabile Ruthenium Polypyridyl Crosslinkers for Hydrogel Formation and Multiplexed, Visible-light Degradation.

Photoresponsive materials afford spatiotemporal control over desirable physical, chemical and biological properties. For advanced applications, there is need for molecular phototriggers that are readily incorporated within larger structures, and spatially-sequentially addressable with different wavelengths of visble light, enabling multiplexing. Here we describe spectrally tunable (λ = 420-530 nm) ruthenium polypyridyl complexes functionalized with two photolabile nitrile ligands that present terminal alkynes for subsequent crosslinking reactions, including hydrogel formation.

Ruthenium-cross-linked hydrogels for rapid, visible-light protein release.

Ruthenium (Ru) polypyridyl complexes are described that present chemically reactive moieties on one or two photolabile ligands for engineering photoresponsive molecules or materials. Ru-cross-linkers can form hydrogels, with proteins or other biomolecules embedded. In this way, the protein is "caged" until released with light.

Ruthenium-Crosslinked Hydrogels with Rapid, Visible-Light Degradation.

Incorporation of photoresponsive molecules within soft materials can provide spatiotemporal control over bulk properties and address challenges in targeted delivery and mechanical variability. However, the kinetics of in situ photochemical reactions are often slow and typically employ ultraviolet wavelengths. Here, we present a novel photoactive crosslinker Ru(bipyridine) (3-pyridinaldehyde) (RuAldehyde), which was reacted with hydrazide-functionalized hyaluronic acid to form hydrogels capable of encapsulating protein cargo.

Kinetics and Photochemistry of Ruthenium Bisbipyridine Diacetonitrile Complexes: An Interdisciplinary Inorganic and Physical Chemistry Laboratory Exercise.

The study of ruthenium polypyridyl complexes can be widely applied across disciplines in the undergraduate curriculum. Ruthenium photochemistry has advanced many fields including dye-sensitized solar cells, photoredox catalysis, light-driven water oxidation, and biological electron transfer. Equally promising are ruthenium polypyridyl complexes that provide a sterically bulky, photolabile moiety for transiently "caging" biologically active molecules.