Molecular Insight into Long-Wavelength Fluorogenic Dye Design: Hydrogen Bond Induces Activation of a Dormant Acceptor.

The detection of chemical or biological analytes in response to molecular changes relies increasingly on fluorescence methods. Therefore, there is a substantial need for the development of improved fluorogenic dyes. In this study, we demonstrated how an intramolecular hydrogen bond activates a dormant acceptor through a charge induction between phenolic hydrogen and a heteroaryl nitrogen moiety.

Synthesis and evaluation of new NIR-fluorescent probes for cathepsin B: ICT versus FRET as a turn-ON mode-of-action.

Recent years have seen tremendous progress in the design and study of molecular imaging geared towards biological and biomedical applications. The expression or activity of specific enzymes including proteases can be monitored by cutting edge molecular imaging techniques. Cathepsin B plays key roles in tumor progression via controlled degradation of extracellular matrix.

Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release.

Polymeric nanocarriers conjugated with low molecular weight drugs are designed in order to improve their efficacy and toxicity profile. This approach is particularly beneficial for anticancer drugs, where the polymer-drug conjugates selectively accumulate at the tumor site, due to the enhanced permeability and retention (EPR) effect. The conjugated drug is typically inactive, and upon its pH- or enzymatically-triggered release from the carrier, it regains its therapeutic activity.

Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles.

Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice.

Modulation of drug resistance in ovarian adenocarcinoma using chemotherapy entrapped in hyaluronan-grafted nanoparticle clusters.

Resistance to anticancer drugs is considered a major cause of chemotherapy failure. One of the major mediators of resistance is the multidrug extrusion pump protein, P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter with broad substrate specificity. In order to bypass this drug resistance mechanism, we have devised phospholipid-based nanoparticle clusters coated with the glycosaminoglycan hyaluronan, the major ligand of CD44, which is upregulated and undergoes different splice variations in many types of cancer cells.

Synthesis and use of QCy7-derived modular probes for the detection and imaging of biologically relevant analytes.

This protocol describes the synthesis of modular turn-ON QCy7-based probes for the detection of biologically relevant analytes, such as hydrogen peroxide, ubiquitous sulfhydryl and β-galactosidase. The probes presented herein are prepared through a simple procedure that involves the preliminary alkylation of 4-hydroxy-isophthalaldehyde with a relevant analyte-responsive protecting group, followed by condensation of the resulting product with 2 equivalents of sulfo-indolium moieties. Evaluation of the turn-ON near-IR fluorescence response to their relevant analytes for the three different QCy7 probes is also reported.

New repertoire of 'donor-two-acceptor' NIR fluorogenic dyes.

Dye molecules with various fluorescent wavelengths are widely used for diagnostic and optical imaging applications. Accordingly, there is a constant demand for fluorogenic dyes with new properties. We have recently developed a novel strategy for the design of long-wavelength fluorescent dyes with a turn-ON option.

A simple FRET-based modular design for diagnostic probes.

In recent years, there has been a massive effort to develop molecular probes with optical modes of action. Probes generally produce detectable signals based on changes in fluorescence properties. Here, we demonstrate the potential of self-immolative molecular adaptors as a platform for Turn-On probes based on the FRET technique.