Over
10 near-IR fluorescent sensitizers were prepared to explore
their properties relevant to potential applications in photodynamic
therapy (PDT). Key properties of these compounds are that they can
be excited around 800 nm, (i) are hydrophilic, (ii) generate singlet
oxygen with acceptable quantum yields, and (iii) are imported into
cancer cells via the organic anion transporter proteins (OATPs). (This
is crucial to tumor localization.) The N-substituents
of these cyanines were varied to adjust their charges and polarities
and to accommodate conjugation to other entities (e.g., biomolecules
or fragments to expand their theranostic modalities). Thus, it was
possible to optimize their photocytotoxicities without compromising
their other desirable characteristics for PDT. Overall, sensitizers
like this have superior characteristics relative to clinically approved
sensitizers for PDT insofar as they can be excited at greater depths
in tissue.
A major restriction on optical imaging techniques is the range of available fluorophores that are compatible with aqueous media without aggregation, absorb light above 750 nm with high extinction coefficients, fluoresce with relatively high quantum yields, and resist photodecomposition. Indocyanine green (ICG or
A
in this paper) is an important example of a fluorophore that fits this description. Other dyes that are becoming increasingly prevalent are select heptamethine cyanine dyes (Cy7) which feature a cyclohexyl framework to rigidify the conjugated alkenes, and
meso
-chlorine substitution; MHI-148 (
B
) is one example.
Methods
: Research described here was initiated to uncover the consequences of a simple isoelectronic substitution to MHI-148 that replaces a cyclohexyl methylene with a dialkyl ammonium fragment. Solubility experiments were carried out in aqueous and cell culture media, photophysical properties including fluorescence quantum yields, brightness and stability were measured. Moreover,
in vivo
pharmacokinetics, distribution and tumor seeking properties were also explored.
Results
: Modification to incorporate dialkyl ammonium fragment leads to a brighter, more photostable fluorophore, with a decreased tendency to aggregation, complementary solubility characteristics, and a lower cytotoxicity.
Conclusion
: All the above-mentioned parameters are favorable for many anticipated applications of the new dye we now call
quaternary cyanine-7
or
QuatCy
.
A near-infrared (NIR) fluorescent sensor 1 composed of an aza-boron-dipyrromethene (aza-BODIPY) core covalently bound to two di-2-picolylamine moieties was conceived for Cu detection in aqueous solutions. Spectroscopic properties and binding abilities with several metal ions were investigated in phosphate buffered saline (pH 7.4): acetonitrile (95 : 5 v/v) with Triton X-100 via fluorometric titrations. The fluorescence of sensor 1 was quenched selectively by cupric ions in the presence of alkali- and transition-metal-ions. A detection limit of 13 ppb was measured for this system, and this is significantly lower than permissible levels of Cu in drinking water according to the guidelines described by the U.S. Environmental Protection Agency (EPA) and by the World Health Organization (WHO). Application of the sensor in detecting Cu in HepG2 cells was demonstrated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.