Mitochondria Targeted AIE Probes for Cancer Phototherapy.

In recent years, mitochondrion (powerhouse of the cells) gained lots of interest as one of the unorthodox targets for futuristic cancer therapy. As a result, novel small molecules were developed to damage and image mitochondria in cancer models. In this context, aggregation-induced emission probes (AIEgens) received immense attention due to their applications in mitochondria-targeted biosensing, imaging, and biomedical theranostics. On the other hand, phototherapy (photodynamic and photothermal) has emerged as a powerful alternative to manage cancer due to its less invasive nature. However, merging these two areas to engineer mitochondria-targeted phototherapeutic probes for cancer diagnosis and treatment has remained a major challenge. In this mini-review, we will outline the development of novel mitochondria-targeted small molecule AIEgens as imaging agents and photosensitizers for photodynamic therapy along with dual photodymanic-phototheramal therapy and chemo-photodynamic therapy. We will also highlight the current challenges in developing mitochondria-targeted photothermal therapy probes for future biomedical theranostic applications to manage cancer.

Illuminating Sub-Cellular Organelles by Small Molecule AIEgens.

Sub-cellular organelles play a critical role in a myriad biological phenomena. Consequently, organelle structures and functions are invariably highjacked in diverse diseases including metabolic disorders, aging, and cancer. Hence, illuminating organelle dynamics is crucial in understanding the diseased states as well as developing organelle-targeted next generation therapeutics. In this review, we outline the novel small molecules which show remarkable aggregation-induced emission (AIE) properties due to restriction in intramolecular motion (RIM). We outline the examples of small molecules developed to image organelles like mitochondria, endoplasmic reticulum (ER), Golgi, lysosomes, nucleus, cell membrane and lipid droplets. These AIEgens have tremendous potential for next-generation phototherapy.

Effects of piperine, cinnamic acid and gallic acid on rosuvastatin pharmacokinetics in rats.

The purpose of this study was to investigate the potential pharmacokinetic interactions with natural products (such as piperine (PIP), gallic acid (GA) and cinnamic acid (CA)) and rosuvastatin (RSV) (a specific breast cancer resistance protein, BCRP substrate) in rats. In Caco2 cells, the polarized transport of RSV was effectively inhibited by PIP, CA and GA at concentration of 50 µM. After per oral (p.o.) coadministration of PIP, CA and GA (10 mg/kg) significantly increased intravenous exposure (AUC(last)) of RSV (1 mg/kg) by 73.5%, 62.9% and 53.3% (p < 0.05), respectively than alone group (control). Compared with the control (alone) group, p.o. coadministration of PIP, CA and GA (10 mg/kg) significantly increased the oral exposure (AUC(last)) of RSV (5 mg/kg) by 2.0-fold, 1.83-fold (p < 0.05) and 2.34 -fold (p < 0.05), respectively. Moreover, the cumulative biliary excretion of RSV (5 mg/kg, p.o.) was significantly decreased by 53.3, 33.4 and 39.2% at the end of 8 h after p.o. co-administration of PIP, CA and GA (10 mg/kg), respectively. Taken together, these results indicate that the natural products such as PIP, CA and GA significantly inhibit RSV transport in to bile and increased the plasma exposure (AUC(last)) of RSV.