AND-gate Dotaz Zobrazit nápovědu
Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules' ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Anticancer drug delivery strategies are designed to take advantage of the differential chemical environment in solid tumors independently, or to high levels of reactive oxygen species (ROS) or to low pH, compared to healthy tissue. Here, the design and thorough characterization of two functionalizable "AND gate" multiresponsive (MR) block amphiphilic copolymers are reported, aimed to take full advantage of the coexistence of two chemical cues-ROS and low pH-present in the tumor microenvironment. The hydrophobic blocks contain masked pH-responsive side chains, which are exposed exclusively in response to ROS. Hence, the hydrophobic polymer side chains will undergo a charge shift in a very relevant pH window present in the extracellular milieu in most solid tumors (pH 5.6-7.2) after demasking by ROS. Doxorubicin (DOX)-loaded nanosized "AND gate" MR polymersomes (MRPs) are fabricated via microfluidic self-assembly. Chemical characterization reveals ROS-dependent pH sensitivity and accelerated DOX release under influence of both ROS and low pH. Treatment of tumor-bearing mice with DOX-loaded nonresponsive and "AND gate" MRPs dramatically decreases cardiac toxicity. The most optimal "AND gate" MRPs outperform free DOX in terms of tumor growth inhibition and survival, shedding light on chemical requirements for successful cancer nanomedicine.
- MeSH
- doxorubicin farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- kyslík MeSH
- micely MeSH
- myši MeSH
- nanočástice * MeSH
- nanomedicína * MeSH
- nosiče léků MeSH
- reaktivní formy kyslíku MeSH
- systémy cílené aplikace léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
293 s. : il.
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- neurovědy
- fyziologie
2, 610, [1] s. : il., tab.
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- dermatovenerologie
- MeSH
- ambulantní péče pracovní síly MeSH
- úhrada služeb Medicare USA MeSH
- Publikační typ
- novinové články MeSH
We show the influence of osteoblastic SAOS-2 cells on the transfer characteristics of nanocrystalline diamond solution-gated field-effect transistors (SGFET) prepared on glass substrates. Channels of these fully transparent SGFETs are realized by hydrogen termination of undoped diamond film. After cell cultivation, the transistors exhibit about 100× increased leakage currents (up to 10nA). During and after the cell delamination, the transistors return to original gate currents. We propose a mechanism where this triggering effect is attributed to ions released from adhered cells, which depends on the cell adhesion morphology, and could be used for cell culture monitoring.
- MeSH
- akční potenciály * MeSH
- biosenzitivní techniky přístrojové vybavení MeSH
- buněčná adheze * MeSH
- diamant chemie MeSH
- elektronické tranzistory * MeSH
- ionty MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádory kostí * MeSH
- osteosarkom * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
