Rational Design of Asymmetric Polymethines to Attain NIR(II) Bioimaging at >1100 nm.

Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λint play key roles. Up to the current stage, the majority of the reported organic NIR(II) emitters belong to those polymethines terminated by two symmetric chromophores. Such a design has proved to have a small λint that greatly suppresses the internal conversion. However, the imposition of symmetric chromophores is stringent, limiting further development of organic NIR(II) dyes in diversity and versatility. Here, we propose a new concept where as far as the emissive state of the any asymmetric polymethines contains more or less equally transition density between two terminated chromophores, λint can be as small as that of the symmetric polymethines. To prove the concept, we synthesize a series of new polymethines terminated by xanthen-9-yl-benzoic acid and 2,4-diphenylthiopyrylium derivatives, yielding AJBF1112 and AEBF1119 that reveal emission peak wavelength at 1112 and 1119 nm, respectively. The quantum yield is higher than all synthesized symmetric polymethines of 2,4-diphenylthiopyrylium derivatives (SC1162, 1182, 1185, and 1230) in this study. λint were calculated to be as small as 6.2 and 7.3 kcal/mol for AJBF1112 and AEBF1119, respectively, proving the concept. AEBF1119 was further prepared as a polymer dot to demonstrate its in vitro specific cellular imaging and in vivo tumor/bone targeting in the NIR(II) region.

A universal strategy for the fabrication of single-photon and multiphoton NIR nanoparticles by loading organic dyes into water-soluble polymer nanosponges.

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes (molar masses of 479.1-1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). The result showed a substantial improvement over the loading of commercial dyes (3.7-50% loading) while preventing their spontaneous aggregation in aqueous solutions. This packaging strategy includes our newly synthesized organic dyes (> 85% loading) designed for OPVs (242), DSSCs (YI-1, YI-3, YI-8), and OLEDs (ADF-1-3, and DTDPTID) applications. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to near-infrared (NIR) emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.

A reporter mouse for non-invasive detection of toll-like receptor ligands induced acute phase responses.

The acute phase response (APR) is a systemic first-line defense against challenges including infection, trauma, stress, and neoplasia. Alteration of acute phase protein (APP) levels in plasma is the most important change during acute phase response. C-reactive protein (CRP), which increases dramatically during inflammation onset, is an indicator of inflammation. To monitor the process of APR, we generated human CRP promoter-driven luciferase transgenic (hCRP-Luc) mice to quantify the hCRP promoter activation in vivo. The naïve female hCRP-Luc mice express low basal levels of liver bioluminescence, but the naïve male hCRP-Luc mice do not. Thus, female hCRP-Luc mice are suitable for monitoring the process of APR. The liver bioluminescence of female hCRP-Luc mice can be induced by several toll-like receptor (TLR) ligands. The expression of liver bioluminescence was highly sensitive to endotoxin stimulation in a dose-dependent manner. On-off-on bioluminescence response was noted in female hCRP-Luc mice upon two endotoxin stimulations one month apart. The LPS-induced bioluminescence of the female hCRP-Luc mice was IL-6-mediated and associated with APP alpha-1-acid glycoprotein expression. In conclusion, the female hCRP-Luc mouse is a non-invasive, sensitive and reusable reporter tool for APR.

Notch 1 signaling pathway effect on implantation competency.

OBJECTIVE: To investigate the relationship between the Notch 1 signaling pathway and the embryo implantation rate. DESIGN: Mouse embryos were cultured in vitro, and implantation competency was quantified. SETTING: Tertiary fertility center of a university teaching hospital. ANIMAL(S): Outbred ICR strain mouse embryos. INTERVENTION(S): The expression of Notch 1 was altered by adding a γ-secretase inhibitor to the culture medium. We quantified the consequent effect on embryo implantation. MAIN OUTCOME MEASURE(S): We measured the messenger RNA level of Notch 1 gene at different embryonic stages, embryo implantation rate under different culture conditions, the amount of Notch 1, and related implantation competency. RESULT(S): Quantitative polymerase chain reaction showed that the expression of Notch 1 increased during the implantation window. Adding γ-secretase inhibitor in the culture medium decreased the percentage of blastocysts in a dose-dependent manner. A Matrigel invasion assay showed that the competency of implantation required adequate expression of Notch 1 intracellular domain. CONCLUSION(S): Expression of Notch 1 at the proper time is required for the competency of embryo implantation; this effect is mediated through regulation of Notch 1 intracellular domain expression.