No abstract

Death receptors (DR4 and DR5) offer attractive targets for cancer treatment because cancer cell death can be induced by apoptotic signal upon binding of death ligands such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with death receptors. Cyclometalated iridium(III) complexes such as fac-Ir(tpy)3 (tpy = 2-(4-tolyl)pyridine) possess a C 3-symmetric structure like TRAIL and exhibit excellent luminescence properties. Therefore, cyclometalated Ir complexes functionalized with DR-binding peptide motifs would be potent TRAIL mimics to detect cancer cells and induce their cell death. In this study, we report on the design and synthesis of C 3-symmetric and luminescent Ir complex-peptide hybrids (IPHs), which possess cyclic peptide that had been reported to bind DR5. The results of 27 MHz quartz-crystal microbalance (QCM) measurements of DR5 with IPHs and costaining experiments of IPHs and anti-DR5 antibody, suggest that IPHs bind with DR5 and undergo internalization into cytoplasm, possibly via endocytosis. It was also found that IPHs induce slow cell death of these cancer cells in a parallel manner to the DR5 expression level. These results indicate that IPHs may offer a promising tool as artificial luminescent mimics of death ligands to develop a new category of anticancer agents that detect and kill cancer cells.

Graphene oxide (GO), due to its 2D planar structure and favorable physical and chemical properties, has been used in different fields including drug delivery. This study aimed to investigate the impact of different process parameters on the average size of drug-loaded PEGylated nano graphene oxide (NGO-PEG) particles using design of experiment (DoE) and the loading of drugs with different molecular structures on an NGO-PEG-based delivery system. GO was prepared from graphite, processed using a sonication method, and functionalized using PEG 6000. Acetaminophen (AMP), diclofenac (DIC), and methotrexate (MTX) were loaded onto NGO-PEG particles. Drug-loaded NGO-PEG was then characterized using dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), XRD. The DLS data showed that the drug-loaded NGO-PEG suspensions were in the size range of 200 nm–1.3 µm. The sonication time and the stirring rate were found to be the major process parameters which affected the average size of the drug-loaded NGO-PEG. FTIR, DSC, XRD, and SEM demonstrated that the functionalization or coating of the NGO occurred through physical interaction using PEG 6000. Methotrexate (MTX), with the highest number of aromatic rings, showed the highest loading efficiency of 95.6% compared to drugs with fewer aromatic rings (diclofenac (DIC) 70.5% and acetaminophen (AMP) 65.5%). This study suggests that GO-based nano delivery systems can be used to deliver drugs with multiple aromatic rings with a low water solubility and targeted delivery (e.g., cancer).