ABSTRACT
A carrier-based, immunogenic cell death (ICD)-eliciting platinum(IV) chemotherapeutic agent was synthesized via complexation between an axially derivatized Pt(IV)-tocopherol and hyaluronan (HA)-tocopherol nanocarrier. The resultant HA-Pt(IV) complex demonstrated antiproliferative activity and induced calreticulin translocation, an indicator of ICD, in murine and human head and neck cancer (HNC) cells. The intratumorally administered HA-Pt(IV) treatments were tolerable and efficacious in both immunocompetent and immunodeficient mice with HNC, partially because of the direct cytotoxicity. Superior efficacy and survival were observed in the immunocompetent group, suggesting a possible Pt(IV)-induced immunological response, which would only manifest in animals with an intact immune system. Subsequent imaging of tumor tissues demonstrated increased macrophage infiltration in the HA-Pt(IV)-treated tumors compared to the nontreated controls and the cisplatin-treated tumors, suggesting favorable inflammatory activation. RNA sequencing of HA-Pt(IV)-treated tumors indicated that carbohydrate and vitamin metabolisms were the most important Kyoto Encyclopedia of Genes and Genomes pathways, and molecular function, biological process, and cellular component were highly enriched gene ontology categories.
Subject(s)
Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Drug Carriers/chemistry , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/metabolism , Hyaluronic Acid/chemistry , Immunogenic Cell Death/drug effects , Organoplatinum Compounds/administration & dosage , Tocopherols/administration & dosage , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Female , Head and Neck Neoplasms/pathology , Humans , Immunocompromised Host , Male , Mice , Mice, Inbred C3H , Mice, Nude , Treatment OutcomeABSTRACT
Gas hydrate is known to have a slowed decomposition rate at ambient pressure and temperatures below the melting point of ice. As hydrate exothermically decomposes, gas is released and water of the clathrate cages transforms into ice. Based on results from the decomposition of three nominally similar methane hydrate samples, the kinetics of two regions, 180-200 and 230-260 K, within the overall decomposition range 140-260 K, were studied by in situ low temperature X-ray powder diffraction. The kinetic rate constants, k(a), and the reaction mechanisms, n, for ice formation from methane hydrate were determined by the Avrami model within each region, and activation energies, E(a), were determined by the Arrhenius plot. E(a) determined from the data for 180-200 K was 42 kJ/mol and for 230-260 K was 22 kJ/mol. The higher E(a) in the colder temperature range was attributed to a difference in the microstructure of ice between the two regions.
