Supramolecular Nanorods of (N-Methylpyridyl) Porphyrin With Captisol: Effective Photosensitizer for Anti-bacterial and Anti-tumor Activities.

Porphyrins, especially the 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin (TMPyP), are well-accepted as photosensitizers due to strong absorption from visible to near-infrared region, good singlet oxygen quantum yields as well as chemical versatility, all of which can be further modulated through planned supramolecular strategies. In this study, we report the construction of supramolecular nanorods of TMPyP dye/drug with captisol [sulfobutylether-ß-cyclodextrin (SBE7ßCD)] macrocycle through host-guest interaction. The availability of four cationic N-methylpyridyl groups favors multiple binding interaction with the captisol host, building an extended supramolecular assembly of captisol and TMPyP. In addition to the spectroscopic characterizations for the assembly formation, the same has been pictured in SEM and FM images as nanorods of ~10 µm in length or more. Complexation of TMPyP has brought out beneficial features over the uncomplexed TMPyP dye; enhanced singlet oxygen yield, improved photostability, and better photosensitizing effect, all supportive of efficient photodynamic therapy activity. The Captisol:TMPyP complex displayed enhanced antibacterial activity toward E. coli under white light irradiation as compared to TMPyP alone. Cell viability studies performed in lung carcinoma A549 cells with light irradiation documented increased cytotoxicity of the complex toward the cancer cells whereas reduced dark toxicity is observed toward normal CHO cells. All these synergistic effects of supramolecular nanorods of Captisol-TMPyP complex make the system an effective photosensitizer and a superior antibacterial and antitumor agent.

Detection, inhibition and disintegration of amyloid fibrils: the role of optical probes and macrocyclic receptors.

Amyloid fibrils are formed by the aberrant aggregation of proteins into highly ordered ß-sheet structures and are believed to be the root cause of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Prion diseases, etc. and have been the subject of extensive biochemical, biophysical and clinical studies. Developing methods for the early detection of fibril formation using optical spectroscopic techniques and inhibition/disintegration of amyloid fibrils/plaques by introducing small molecules have been a major challenge to establish a clinically facile therapeutic intervention to combat these neurodegenerative diseases. This feature article provides an account of the recent reports from different research groups, including ours, on the optical detection, and inhibition/disintegration of mature fibrils using fluorescent probes and macrocyclic hosts such as cucurbiturils, calixarenes and cyclodextrins. Site specific or spectrally distinct fluorescence emission from a large number of fluorophores in a broad spectral region has been used to detect the fibrillation of different proteins/peptides, mainly insulin, α-synuclein, transthyretin, barstar, lysozyme, Aß40 peptide, etc. On the one hand, while macrocyclic receptors modify the inter-protein interactions through molecular recognition of amino acid residues leading to the inhibition of amyloid fibrillation, on the other hand, one of the cavitands, p-sulfonatocalixarenes, has been demonstrated to cause the disintegration of mature fibrils, effectively through surface charge interactions, which destabilize the extended fibrillar structure into soluble or fine particles. Beneficially, the presence of extrinsic p-sulfonatocalix[4/6]arenes did not introduce any additional toxicity to the cell viability, which advocates its potential utility as a therapeutic for amyloidosis.

Stimuli-Responsive Cucurbit[7]uril-Mediated BSA Nanoassembly for Uptake and Release of Doxorubicin.

We report the construction of a non-toxic nanoassembly of bovine serum albumin (BSA) protein and the cucurbit[7]uril macrocycle as well as its stimuli-responsive breakage with adamantylamine or pH, which restores the protein structure and recognition properties. The assembly showed efficient loading and controlled release of a standard drug, doxorubicin (DOX), and the same was validated in live cells. The cell viability studies documented that the DOX-loaded assembly mask the cytotoxicity of DOX and the toxicity can be revived at the target on demand, triggering its therapeutic activation. This is found to be more effective in the cancer cells. In addition, such host-assisted protein assemblies are also highly promising for stabilizing/protecting the native protein structure, a viable approach to prevent/inhibit protein misfolding and aggregation.

Inhibition and disintegration of insulin amyloid fibrils: a facile supramolecular strategy with p-sulfonatocalixarenes.

We reveal the ability of p-sulfonatocalix[4/6]arene to effectively inhibit the fibril formation in human insulin and demonstrate its potential to disintegrate the mature fibrils, a promising supramolecular strategy to combat amyloidosis.

Targeting G-quadruplex structures with extrinsic fluorogenic dyes: promising fluorescence sensors.

The research on the G-quadruplex DNAs has received much attention in recent years and numerous reports appeared probing their detection, structure, stability, reactivity, selectivity, etc. for the chemical intervention of their biological activity or sensor applications. This feature article provides an account of the recent reports from different research groups on the intriguing fluorescence properties showcased by certain fluorogenic dyes upon their binding to the G-quadruplex DNAs. Aptly, these selective and sensitive emission features demonstrated with structure specific G-quadruplex DNAs have been turned into label-free fluorescence-based detection methods for various metal ions and small biomolecules, down to the pico molar range, having promising bio-analytical applications. While the in vivo formation of G-quadruplexes is dynamically sensitive to the cell cycle, in tandem with the in vitro applications, it is essential to understand the factors that affect chemical, biological and genetic roles of the G-quadruplex structures plausible along the human genome. Towards this, the recent findings on the quantitative visualization of the quadruplex structures in the human cells using immunofluorescent probes open up avenues to explore highly specific quadruplex responsive agents for diagnostic and therapeutic applications, especially to develop a clinically viable method for cancer treatment.