The Role of Small Peptides in Cancer Physiology and Chemotherapy

The targeting of proven anticancer drugs specifically to cancer cells would provide a unique opportunity to restrict neoplasms without damaging the cancer patient. The present research utilizes the phenomenon of illicit transport, i.e. the coupling of normally impermeant metabolites to permeant metabolites, in targeting the drug melphalan to mouse Ehrlich ascites tumor cells. The dipeptide beta-alanyl-melphalan was synthesized and tested in vitro for toxicity towards mouse Ehrlich ascites tumor cells, mouse liver cells, and mouse 3T3 embryonic cells. The parent compound, melphalan, was used as a control treatment. In addition, both melphalan and beta-alanyl-melphalan were utilized in in vivo chemotherapeutic assays to assess the efficacy of both drugs to restrict tumor cell growth in a mouse model system. The dipeptide, beta-alanyl-melphalan, was synthesized using standard liquid synthesis procedures and assayed for purity and stability by high performance liquid chromatography. The peptide was shown to be greater than 85% pure and was significantly more stable at 37\sp\circC than melphalan, exhibiting a half-life in solution of 607.71 minutes. The half-life of melphalan under similar conditions was 105.21 minutes. The inclusion of proteins in solutions of melphalan increased the stability of this drug, providing for a half-life of 176.72 minutes. Both melphalan and beta-alanyl-melphalan were stable at 0\sp\circC. In in vitro toxicity assays, melphalan was shown to be toxic to all three cell systems studied, whereas beta-alanyl-melphalan was toxic only towards the Ehrlich ascites tumor cells and the 3T3 fibroblast cells. The dipeptide containing melphalan was not toxic to the mouse liver cells at concentrations up to 0.1 mM. Toxicity assays included assessment of both plasma membrane permeability and cell proliferation after drug treatment. Morphological studies, using scanning and transmission electron microscopy as well as light microscopy, of treated cells corroborated the toxicity assays, revealing reduced cell numbers, aberrant cell morphologies, and cell destruction where drug treatment had been demonstrated to alter membrane integrity and/or cell proliferation was observed, i.e. beta-alanyl-melphalan treatment of mouse liver cells, cellular morphologies were demonstrated to be similar to nontreated liver cells. In vivo chemotherapy assays, using Ehrlich ascites tumor cells injected into the abdominal cavity of mice, revealed that melphalan, at concentrations of 5 and 10 mg/kg, was an effective anticancer drug providing for T/C rations of 179 and 193 respectively. The dipeptide, beta-alanyl-melphalan, was also an effective anticancer drug, exhibiting reduced toxicity towards the tumor bearing animal when compared to the parent drug melphalan, providing for T/C rations of 152 at a drug concentration of 40 mg/kg. Neither drug had observable effects on animal activities, i.e. food and water consumption, yet significantly restricted tumor cell growth as assessed by increasing body weights and survival times of tumor bearing mice

Perovskite materials as superior and powerful platforms for energy conversion and storage applications

In order to meet the continuously growing demand for clean energy, a plethora of advanced materials have been exploited for energy storage applications. Among these materials, perovskites belong to a relatively new family of compounds with the structural formula of ABX3. These compounds exhibit a variety of electrical, optical, and electronic properties to adopt them for a variety of energy conversion and storage applications. The present review highlights the multifaceted nature of perovskite materials by covering a brief background, common crystallographic structures, and the importance of doping with different elements. Our discussion is extended further on the strategic energy applications of perovskites in modern devices such as fuel cells, lithium batteries, supercapacitors, LEDs, and solar cells.</p