Comparing a thioglycosylated chlorin and phthalocyanine as potential theranostic agents.

Herein we describe the design, efficient synthesis, and photophysical properties of two macrocycle dyes for cancer theranostics. This study compares a glycosylated chlorin with a glycosylated phthalocyanine designed to specifically target cancer, wherein the photophysical properties enable both fluorescence imaging and the sensitization of the formation of reactive oxygen species (ROS) for photodynamic therapy. Both the compounds show low darktoxicity (IC50 > 100 µM). The glycosylated phthalocyanine showed low phototoxicity (IC50 > 100 µM) while glycosylated chlorin showed high phototoxicity (IC50 = 1-2 µM). ZnPcGlc8 has low solubility and also form aggregates in aqueous media, thus resulting in minimal uptake in two different human breast cancer cell lines: MDA-MB-231 and MCF-7. The glycosylated chlorin however was efficiently taken up by these two cell lines, thus allows fluorescence imaging in cells and in xenograft tumor model in mice. In this study, we find that the chlorin conjugate is the more promising theranostic agent.

Direct Imaging of Drug Distribution and Target Engagement of the PARP Inhibitor Rucaparib.

Poly(ADP-ribose)polymerase (PARP) inhibitors have emerged as potent antitumor drugs. Here, we describe the intrinsic fluorescence properties of the clinically approved PARP inhibitor rucaparib and its potential to directly measure drug distribution and target engagement-a critical factor for understanding drug action and improving efficacy. Methods: We characterized the photophysical properties of rucaparib and determined its quantum yield and lifetime. Using confocal microscopy and flow cytometry, we imaged the intracellular distribution of rucaparib and measured uptake and release kinetics. Results: Rucaparib has an excitation/emission maximum of 355/480 nm and a quantum yield of 0.3. In vitro time-lapse imaging showed accumulation in cell nuclei within seconds of administration. Nuclear rucaparib uptake increased with higher PARP1 expression, and we determined an intracellular half-life of 6.4 h. Conclusion: The label-free, intrinsic fluorescence of rucaparib can be exploited to interrogate drug distribution and target binding, critical factors toward improving treatment efficacy and outcome.

Immunostimulatory lipid nanoparticles from herbal medicine.

Reproducibility is an important issue in biological characterization of drug candidates and natural products. It is not uncommon to encounter cases in which supposedly the same sample exhibits very different biological activities. During our characterization of macrophage-stimulatory lipids from herbal medicine, it was found that the potency of these lipids could vary substantially from experiment to experiment. Further analysis of this reproducibility issue led to the discovery of solvent-dependent nanoparticle formation by these lipids. While larger nanoparticles (approximately 100 nm) of these lipids showed modest macrophage-stimulatory activity, smaller nanoparticles (<10 nm) of the same lipids exhibited substantially higher potency. Thus, the study revealed an unexpected link between nanoparticle formation and macrophage-stimulatory activity of plant lipids. Although nanoparticles have been extensively studied in the context of vehicles for drug delivery, our finding indicates that drugs themselves can form nanoassemblies, and their biological properties may be altered by the way they assemble.

Self-organization of a new fluorous porphyrin and C60 films on indium-tin-oxide electrode.

The highly fluorinated alkyl moieties of a new porphyrin drive the self-organization of thin films with C(60) on ITO electrodes.

Two color RNA intercalating probe for cell imaging applications.

Here we report on a phenanthridine derivative which has a covalently linked fluorescein molecule in order to increase the light absorption and hence fluorescence signal intensity when bound to duplex RNA. Steady-state fluorescence shows that the energy transfer efficiency from the fluorescein to the phenanthridine fluorophore is approximately 77%, which results in the probe being over 5x brighter than other phenanthridine derivatives when bound to RNA. Due to the relatively long lifetime (approximately 20 ns) of the probe, time-resolved fluorescence is used to increase the signal to background ratio in cell growth medium from 7 (steady-state value) to over 40. Moreover, fluorescence images of cells containing the probe show that the fluorescein signal is readily apparent along with that of the intercalated fluorophore, allowing this probe to be used as a dual color probe which simultaneously reports the probes' location and that of RNA.

Efficient microwave-assisted synthesis of amine-substituted tetrakis(pentafluorophenyl)porphyrin.

We report an efficient and rapid means for the synthesis of tetrakis(pentafluorophenyl)porphyrin (TPPF(20)) derivatives by microwave irradiation in an environmentally acceptable solvent. The selective displacement of the para-fluorine groups in TPPF(20) by primary amines occurs in yields between 70 and 95%. This method demonstrates that TPPF(20) is an ideal platform for the rapid formation of porphyrin conjugates for therapeutic, catalytic, and other applications. [reaction: see text]

A benchtop method for the fabrication and patterning of nanoscale structures on polymers.

A benchtop method for the facile production of nanoscale metal structures on polymers is demonstrated. This approach allows for the design and patterning of a wide range of metallic structures on inexpensive polymer surfaces, affording the fabrication of nanoscaled platforms for use in the design of sensors, actuators, and disposable electronic and photonic devices. Numerous structures, from simple nanowires to multilayered metallic gratings, are demonstrated, with sizes ranging from microns to the nanoscale. The process involves molding a malleable metal film deposited on a rigid substrate such as mica, by the compression of a plastic polymer stamp with the desired pattern against the metal film. While under compression, an etchant is then used to modify the metal. Upon separation of the stamp from the support, micro- to nanoscaled metallic structures are found on the stamp and/or on the substrate. The sizes of the structures formed depend on the sizes of the features on the stamp but can be fine-tuned by about 4-fold through variations in both pressure and duration of etching. Also, depending on the processing, multiple dimension metallic structures can be obtained simultaneously in a single stamping procedure. The metallic structures formed on the stamp can also be subsequently transferred to another surface allowing for the construction of multilayered materials such as band gap gratings or the application of electrical contacts. Using this approach, fabrication of both simple and complex micro- to nanoscaled structures can be accomplished by most any researcher as even the grating structure of commercial compact disks may be used as stamps, eliminating the requirement of expensive lithographic processes to form simple structures.