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Functionalization of mesoporous organosilica nanocarrier for pH/glutathione dual-responsive drug delivery and imaging of cancer therapy process.

Talanta 2018 January 16
A multifunctional drug nanocarrier is developed by incorporating acetaldehyde-modified-cystine (AMC) into mesoporous organosilica nanoparticles (MONs), shortly termed as MONs-AMC. The anticancer drug doxorubicin (DOX) links directly to MONs-AMC through electrostatic interaction between DOX and AMC to produce a conjugate, MONs-AMC-DOX, with a drug loading efficiency of 26.24 ± 1.35%, corresponding to a loading capacity of 0.26 ± 0.01mgmg-1 for DOX. Schiff base AMC contains a -S-S- bond and two -C˭N- bonds which cleave in the presence of certain level of GSH and in an acidic medium, providing MONs-AMC-DOX the capability for triggering pH and glutathione (GSH) dual-responsive drug release. Further, the self-fluorescent nature of AMC offers the tracing capability without the need of fluorescent label, which facilitates real-time tracing of the drug delivery and cancer therapy process. With 10mmolL-1 GSH and at pH 5.0, a drug release efficiency of 52.27 ± 2.84% is achieved. The intracellular drug release process is traced with confocal laser scanning microscope by monitoring the green fluorescence of MONs-AMC-DOX and red fluorescence of DOX with excitation at 408nm and 488nm, respectively. The drug loaded nanocarriers exhibit a time-dependent cellular uptake behavior, providing an enhanced therapeutic effect to A549 cancer cells.

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