Involvement of Lipids in the Physicochemical and In Vitro Characteristics of Polymer-lipid Nanoparticles in Cancer Cell Models

Polymer-lipid nanoparticles (PLN) have been a focus in cancer chemotherapy research due to their potential for targeting tumour cells, overcoming drug resistance and reducing toxicity. This work explores the (1) impact of “lipid” component properties and formulation parameters on PLN physicochemical properties and in vitro cytotoxicity using statistical design-of-experiments, and (2) mechanisms of PLN cell entry and organelle distribution, and response to lysosomal environments. These analyses show effects of melting point and chemical structure of multiple fatty acids/esters, and long heat exposure on PLN properties. As a result, a robust PLN system was optimized as a doxorubicin (DOX) delivery system for human glioblastoma U87-MG-RED-FLuc cells. This PLN system demonstrated intracellular internalization by multiple cell mechanisms. Furthermore, mechanistic studies examined the role of not only the optimized PLN in glioblastoma cells, but also in a previously-studied myristic acid-based PLN in breast tumour cells on improved potency over free drug.M.Sc.2021-07-28 00:00:0

Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives

COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.Peer Reviewe