Enabling In Vivo Photocatalytic Activation of Rapid Bioorthogonal Chemistry by Repurposing Silicon-Rhodamine Fluorophores as Cytocompatible Far-Red Photocatalysts.
Chuanqi WangHe ZhangTao ZhangXiaoyu ZouHui WangJulia E RosenbergerRaghu VannamWilliam S TroutJonathan B GrimmLuke D LavisColin ThorpeXinqiao JiaZibo LiJoseph M FoxPublished in: Journal of the American Chemical Society (2021)
Chromophores that absorb in the tissue-penetrant far-red/near-infrared window have long served as photocatalysts to generate singlet oxygen for photodynamic therapy. However, the cytotoxicity and side reactions associated with singlet oxygen sensitization have posed a problem for using long-wavelength photocatalysis to initiate other types of chemical reactions in biological environments. Herein, silicon-Rhodamine compounds (SiRs) are described as photocatalysts for inducing rapid bioorthogonal chemistry using 660 nm light through the oxidation of a dihydrotetrazine to a tetrazine in the presence of trans-cyclooctene dienophiles. SiRs have been commonly used as fluorophores for bioimaging but have not been applied to catalyze chemical reactions. A series of SiR derivatives were evaluated, and the Janelia Fluor-SiR dyes were found to be especially effective in catalyzing photooxidation (typically 3%). A dihydrotetrazine/tetrazine pair is described that displays high stability in both oxidation states. A protein that was site-selectively modified by trans-cyclooctene was quantitatively conjugated upon exposure to 660 nm light and a dihydrotetrazine. By contrast, a previously described methylene blue catalyst was found to rapidly degrade the protein. SiR-red light photocatalysis was used to cross-link hyaluronic acid derivatives functionalized by dihydrotetrazine and trans-cyclooctenes, enabling 3D culture of human prostate cancer cells. Photoinducible hydrogel formation could also be carried out in live mice through subcutaneous injection of a Cy7-labeled hydrogel precursor solution, followed by brief irradiation to produce a stable hydrogel. This cytocompatible method for using red light photocatalysis to activate bioorthogonal chemistry is anticipated to find broad applications where spatiotemporal control is needed in biological environments.
Keyphrases
- visible light
- hyaluronic acid
- photodynamic therapy
- drug delivery
- fluorescent probe
- endothelial cells
- quantum dots
- fluorescence imaging
- wound healing
- protein protein
- type diabetes
- binding protein
- adipose tissue
- living cells
- skeletal muscle
- mass spectrometry
- magnetic resonance imaging
- gold nanoparticles
- amino acid
- structure activity relationship
- computed tomography
- light emitting
- ultrasound guided
- high resolution
- pluripotent stem cells
- liquid chromatography