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A Novel H₂O₂ Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy.

ABSTRACT: Carbon monoxide (CO) gas therapy is a promising cancer treatment. However, gas delivery to the tumor site remains problematic. Proper tunable control of CO release in tumors is crucial to increasing the efficiency of CO treatment and reducing the risk of CO poisoning. To overcome such challenges, we designed ZCM, a novel stable nanotechnology delivery system comprising manganese carbonyl (MnCO) combined with anticancer drug camptothecin (CPT) loaded onto a zeolitic imidazole framework-8 (ZIF-8). After intravenous injection, ZCM gradually accumulates in cancerous tissues, decomposing in the acidic tumor microenvironment, releasing CPT and MnCO. CPT acts as a chemotherapy agent destroying tumors and producing copious H₂O₂. MnCO can react with the H₂O₂ to generate CO, powerfully damaging the tumor. Both in vitro and in vivo experiments indicate that the ZCM system is both safe and has excellent tumor inhibition properties. ZCM is a novel system for CO controlled release, with significant potential to improve future cancer therapy.

SUBMITTER: Li Y

PROVIDER: S-EPMC8496405 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This work illustrates the potential of using atomistic molecular dynamics (MD) and grand-canonical Monte Carlo (GCMC) simulations prior to experiments in order to pre-screen candidate membrane structures for gas separation, under harsh conditions of temperature and pressure. It compares at 300 °C and 400 °C the CO2/CH4 and CO2/N2 sieving properties of a series of hybrid networks based on inorganic silsesquioxanes hyper-cross-linked with small organic PMDA or 6FDA imides. The inorganic precursors are the octa(aminopropyl)silsesquioxane (POSS), which degrades above 300 °C, and the octa(aminophenyl)silsesquioxane (OAPS), which has three possible meta, para or ortho isomers and is expected to resist well above 400 °C. As such, the polyPOSS-imide networks were tested at 300 °C only, while the polyOAPS-imide networks were tested at both 300 °C and 400 °C. The feed gas pressure was set to 60 bar in all the simulations. The morphologies and densities of the pure model networks at 300 °C and 400 °C are strongly dependent on their precursors, with the amount of significant free volume ranging from ~2% to ~20%. Since measurements at high temperatures and pressures are difficult to carry out in a laboratory, six isomer-specific polyOAPS-imides and two polyPOSS-imides were simulated in order to assess their N2, CH4 and CO2 permselectivities under such harsh conditions. The models were first analyzed under single-gas conditions, but to be closer to the real processes, the networks that maintained CO2/CH4 and CO2/N2 ideal permselectivities above 2 were also tested with binary-gas 90%/10% CH4/CO2 and N2/CO2 feeds. At very high temperatures, the single-gas solubility coefficients vary in the same order as their critical temperatures, but the differences between the penetrants are attenuated and the plasticizing effect of CO2 is strongly reduced. The single-gas diffusion coefficients correlate well with the amount of available free volume in the matrices. Some OAPS-based networks exhibit a nanoporous behavior, while the others are less permeable and show higher ideal permselectivities. Four of the networks were further tested under mixed-gas conditions. The solubility coefficient improved for CO2, while the diffusion selectivity remained similar for the CO2/CH4 pair and disappeared for the CO2/N2 pair. The real separation factor is, thus, mostly governed by the solubility. Two polyOAPS-imide networks, i.e., the polyorthoOAPS-PMDA and the polymetaOAPS-6FDA, seem to be able to maintain their CO2/CH4 and CO2/N2 sieving abilities above 2 at 400 °C. These are outstanding performances for polymer-based membranes, and consequently, it is important to be able to produce isomer-specific polyOAPS-imides for use as gas separation membranes under harsh conditions.

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A Novel H₂O₂ Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy.

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