Engineered pH-Responsive Mesoporous Carbon Nanoparticles for Drug Delivery
journal contributionposted on 17.03.2020, 17:06 by Miguel Gisbert-Garzarán, Julia C. Berkmann, Dimitra Giasafaki, Daniel Lozano, Konstantinos Spyrou, Miguel Manzano, Theodore Steriotis, Georg N. Duda, Katharina Schmidt-Bleek, Georgia Charalambopoulou, María Vallet-Regí
In this work, two types of mesoporous carbon particles with different morphology, size, and pore structure have been functionalized with a self-immolative polymer sensitive to changes in pH and tested as drug nanocarriers. It is shown that their textural properties allow significantly higher loading capacity compared to typical mesoporous silica nanoparticles. In vial release experiments of a model Ru dye at pH 7.4 and 5 confirm the pH-responsiveness of the hybrid systems, showing that only small amounts of the cargo are released at physiological pH, whereas at slightly acidic pH (e.g., that of lysosomes), self-immolation takes place and a significant amount of the cargo is released. Cytotoxicity studies using human osteosarcoma cells show that the hybrid nanocarriers are not cytotoxic by themselves but induce significant cell growth inhibition when loaded with a chemotherapeutic drug such as doxorubicin. In preparation of an in vivo application, in vial responsiveness of the hybrid system to short-term pH-triggering is confirmed. The consecutive in vivo study shows no substantial cargo release over a period of 96 h under physiological pH conditions. Short-term exposure to acidic pH releases an experimental fluorescent cargo during and continuously after the triggering period over 72 h.
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Cytotoxicity studiesvivo studypH 7.4cargo release96 hShort-term exposurevivo applicationtextural propertiesmodel Ru dyeself-immolative polymerDrug Deliverycell growth inhibition72 hchemotherapeutic drugvial responsivenessloading capacitypore structureosteosarcoma cells showmesoporous silica nanoparticlesdrug nanocarriersacidic pH releasesmesoporous carbon particlesEngineered pH-Responsive Mesoporous Carbon Nanoparticlesvial release experimentspH conditionsacidic pH