Aggregation-Induced Emission of Contorted Polycondensed Aromatic Hydrocarbons Made by Edge Extension Using a Palladium-Catalyzed Cyclopentannulation Reaction.

Contorted polycyclic aromatic hydrocarbons (PAHs), CPA1-2 and CPB1-2, bearing peripheral five-membered rings were synthesized employing a palladium-catalyzed cyclopentannulation reaction using specially designed diaryl acetylene synthons TPE and TPEN with commercially available dibromo- anthracene DBA and bianthracene DBBA derivatives. The resulting target compounds CPA1-2 and CPB1-2 were isolated in excellent yield and found to be highly soluble in common organic solvents, which allowed for their structural characterization and investigation of the photophysical properties, disclosing their aggregation-induced emission (AIE) properties in THF at selective concentration ranges of water fractions in the solvent mixture. Examination of the contorted PAH structures by means of density functional theory (DFT) revealed higher electronic conjugation in the more rigid and planar anthracene-containing CPA1-2 derivatives when compared to the twisted bianthracene-bearing moieties CBPA1-2 with HOMO-LUMO bandgaps (ΔE) of ∼2.32 eV for the former PAHs and ∼2.78 eV for the latter ones.

Nanoparticles for super-resolution microscopy: intracellular delivery and molecular targeting.

Following an overview of the approaches and techniques used to acheive super-resolution microscopy, this review presents the advantages supplied by nanoparticle based probes for these applications. The various clases of nanoparticles that have been developed toward these goals are then critically described and these discussions are illustrated with a variety of examples from the recent literature.

Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania.

Leishmaniasis, a vector-borne disease, is caused by intracellular parasite Leishmania donovani. Unlike most intracellular pathogens, Leishmania donovani are lodged in parasitophorous vacuoles and replicate within the phagolysosomes in macrophages. Effective vaccines against this disease are still under development, while the efficacy of the available drugs is being questioned owing to the toxicity for nonspecific distribution in human physiology and the reported drug-resistance developed by Leishmania donovani. Thus, a stimuli-responsive nanocarrier that allows specific localization and release of the drug in the lysosome has been highly sought after for addressing two crucial issues, lower drug toxicity and a higher drug efficacy. We report here a unique lysosome targeting polymeric nanocapsules, formed via inverse mini-emulsion technique, for stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line. A benign polymeric backbone, with a disulfide bonding susceptible to an oxidative cleavage, is utilized for the organelle-specific release of miltefosine. Oxidative rupture of the disulfide bond is induced by intracellular glutathione (GSH) as an endogenous stimulus. Such a stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line over a few hours helped in achieving an improved drug efficacy by 200 times as compared to pure miltefosine. Such a drug formulation could contribute to a new line of treatment for leishmaniasis.

Recent Advances in Fluorescent Probes for Detection of HOCl and HNO.

It is known that reactive oxygen (ROS) and nitrogen (RNS) species play a diverse role in various biological processes, such as inflammation, signal transduction, and neurodegenerative injury, apart from causing various diseases caused by oxidative and nitrosative stresses, respectively, by ROS and RNS. Thus, it is very important to quantify the concentration level of ROS and RNS in live cells, tissues, and organisms. Various small-molecule-based fluorescent/chemodosimetric probes are reported to quantify and map the effective distribution of ROS/RNS under in vitro/in vivo conditions with a great spatial and temporal resolution. Such reagents are now appreciated as an excellent tool for aiding breakthroughs in modern redox biology. This mini-review is a brief, but all-inclusive, account of such molecular probes that have been developed recently.

Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy.

Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm-2) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)2) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH3)2. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer.

Small Molecule as Fluorescent Probes for Monitoring Intracellular Enzymatic Transformations.

All cellular processes are the results of synchronized actions of several intracellular biochemical pathways. Recent emphasis is to visualize such pathways using appropriate small molecular reagents, dye-labeled proteins, and genetically encoded fluorescent biosensors that produce a luminescence ON response either on selective binding or on reacting with an analyte that is produced through a specific biochemical/enzymatic transformation. Studying such enzymatic processes by probing the fluorescence response as the read-out signal is expected to provide important insights into crucial biochemical transformations induced by an enzyme in its native form. Many of such studies are extended for monitoring enzymatic transformations under in vitro or in vivo condition. A few of the recent reports reveal that such molecular probes are even capable of quantifying abnormal levels of enzymes in real-time and is linked to the key area of clinical diagnostics and chemical biology. A synchronized analysis of all such reports helps in developing a rationale for designing purpose-built molecular probes or chemodosimeters as well as newer reagents for studying crucial enzymatic process or quantification of the respective enzyme. In this review, an attempt will be there to highlight several recent bioimaging reagents and studies that have provided insights into crucial biochemical or enzymatic transformations.