Glucocorticoid receptor mediated sensitization of colon cancer to photodynamic therapy induced cell death.

Photodynamic therapy (PDT) is a clinically approved, non-invasive alternate cancer therapy. A synthetic glucocorticoid (GC), dexamethasone (Dex) has previously been demonstrated to sensitize cancer cells to chemotherapy. However, to the best of our knowledge, the sensitization effect of GCs on PDT has not yet been investigated. We hypothesized that glucocorticoid receptor (GR) targeting can selectively make cancer cells more sensitive to PDT treatment, as PDT induces hypoxia wherein GR-activity gets enhanced. In addition, Dex was reported to act against the PDT-induced cell survival pathways like HIF-1α, NRF2, NF-κB, STAT3 etc. Thus, both the treatments can complement each other and may result in increasing the effectiveness of combination therapy. Hence, in this study, we developed liposomal formulations of our previously reported PDT agent P-Nap, either alone (D1P-Nap) or in combination with Dex (D1XP-Nap) to elucidate the sensitization effect. Interestingly, our RT-PCR results in hypoxic conditions showed down-regulation of HIF-1α and over expression of GR-activated genes for glucose-6-phosphatase (G6Pase) and PEPCK enzymes, indicating prominent GR-transactivation. We also observed higher phototoxicity in CT26.WT cells treated with D1XP-Nap PDT under hypoxic conditions as compared to normoxic conditions. These effects were reversed when cells were pre-treated with RU486, a competitive inhibitor of GCs. Moreover, our in vivo findings of subcutaneous tumor model of Balb/C mice for colon cancer revealed a significant decrease in tumor volume as well as considerable enhancement in the survivability of PDT treated tumor-bearing mice when Dex was present in the formulation. A high Bax/Bcl-xL ratio, high p53 expression, enhanced E-cadherin expression and down-regulation of pro-tumorigenic transcription factors NF-κB and c-Myc were found in tumor lysates from mice treated with D1XP-Nap under PDT, indicating GR-mediated sensitization of the tumor to PDT-induced cell death and enhancement of life-span for tumor bearing mice.

Phenothiazine functional materials for organic optoelectronic applications.

Phenothiazine (PTZ) is one of the most extensively investigated S, N heterocyclic aromatic hydrocarbons due to its unique optical, electronic properties, flexibility of functionalization, low cost, and commercial availability. Hence, PTZ and its derivative materials have been attractive in various optoelectronic applications in the last few years. In this prospective, we have focused on the most significant characteristics of PTZ and highlighted how the structural modifications such as different electron donors or acceptors, length of the π-conjugated system or spacers, polar or non-polar chains, and other functional groups influence the optoelectronic properties. This prospective provides a recent account of the advances in phenothiazine derivative materials as an active layer(s) for optoelectronic (viz. dye sensitized solar cells (DSSCs), perovskite solar cells (PSCs), organic solar cells (OSCs), organic light-emitting diodes (OLEDs), organic field-effect transistor (OFETs), chemosensing, nonlinear optical materials (NLOs), and supramolecular self-assembly applications. Finally, future prospects are discussed based on the structure-property relationship in PTZ-derivative materials. This overview will pave the way for researchers to design and develop new PTZ-functionalized structures and use them for various organic optoelectronic applications.