Biomedical-Optical-Window Tailored Cyanines for Steerable Inflammatory Bowel Disease Theranostic.

Tailored photophysical properties and chemical activity is the ultimate pursuit of functional dyes for in vivo biomedical theranostics. In this work, the independent regulation of the absorption and fluorescence emission wavelengths of heptamethine cyanines is reported. These dyes retain near-infrared fluorescence emission (except a nitro-modified dye) while feature variable absorption wavelengths ranging from 590 to 860 nm. This enables to obtain customized functional dyes that meet the excitation and fluorescence wavelength requirements defined by the optical properties of tissues for in vivo biomedical applications. Typically, a nitro-modified photothermal active derivative Cy-Mu-7-9 is used, which features strong absorption at 810 nm in PBS, a wavelength that balanced the tissue penetration depth and non-specific photothermal effect, to realize non-destructive inflammatory bowel disease (IBD) therapy via photothermal induced up-regulation of heat shock protein 70 in the intestinal epithelial cells. The corresponding amino-modified dye Cy-Mu-7-9-NH2, which can be formed in health enteric cavity by Cy-Mu-7-9 after oral administration, is a fluorescence compound with the emission of 800 nm in PBS. Based on the IBD sensitive transformation of Cy-Mu-7-9 and Cy-Mu-7-9-NH2, in vivo IBD theranostic and therapeutic effect evaluation is realized via the synergy of fluorescence imaging and photothermal therapy for the first time.

Fluorimetric Tool to Discriminate Glomerular and Tubular Injuries In Vivo.

The etiology and pathological complexity of acute kidney injury (AKI) pose great challenges for early diagnosis, typing, and personalized treatment. It is an important reason for poor prognosis and high mortality of AKI. In order to provide a relatively noninvasive diagnostic and typing method for AKI, we proposed the pathological changes of albumin permeability after glomerular injury and reabsorption efficiency after tubular injury as potential entry points. Thus, a renal tubule labeling fluorescent dye which features albumin concentration-related fluorescence intensity was used to fit these pathological changes. Utilizing this fluorescence assay, we realized urinary tract obstruction imaging as early as 12 h after morbidity. For glomerular and tubular injury discrimination, compared to a healthy control, membranous nephropathy as a representative glomerular injury resulted in enhanced fluorescence intensity of the kidney due to increased albumin penetration, while renal tubular injury caused insufficient dye reabsorption to exhibit weakened fluorescence intensity. The significant differences demonstrated the feasibility of this approach for fluorescence imaging-based AKI typing in vivo.

Enlarging the Stokes Shift by Weakening the π-Conjugation of Cyanines for High Signal-to-Noise Ratiometric Imaging.

The signal-to-noise ratio (SNR) is one of the key features of a fluorescent probe and one that often defines its potential utility for in vivo labeling and analyte detection applications. Here, it is reported that introducing a pyridine group into traditional cyanine-7 dyes in an asymmetric manner provides a series of tunable NIR fluorescent dyes (Cy-Mu-7) characterized by enhanced Stokes shifts (≈230 nm) compared to the parent cyanine 7 dye (<25 nm). The observed Stokes shift increase is ascribed to symmetry breaking of the Cy-Mu-7 core and a reduction in the extent of conjugation. The fluorescence signals of the Cy-Mu-7 dyes are enhanced upon confinement within the hydrophobic cavity of albumin or via spontaneous encapsulation within micelles in aqueous media. Utilizing the Cy-Mu-7, ultra-fast in vivo kidney labeling in mice is realized, and it is found that the liver injury will aggravate the burden of kidney by monitoring the fluorescence intensity ratio of kidney to liver. In addition, Cy-Mu-7 could be used as efficient chemiluminescence resonance energy transfer acceptor for the reaction between H2 O2 and bisoxalate. The potential utility of Cy-Mu-7 is illustrated via direct monitoring fluctuations in endogenous H2 O2 levels in a mouse model to mimic emergency room trauma.