Fabrication of a pH/redox-triggered mesoporous silica-based nanoparticle with microfluidics for anti-cancer drugs doxorubicin and paclitaxel co-delivery

A pH/redox-triggered mesoporous silica nanoparticle (MSN)-based nano-platform has been fabricated for doxorubicin/paclitaxel (DOX/PTX) co-delivery. In this drug-delivery system (DDS), PTX is covalently attached to the surface of DOX loaded MSN via a linker with disulfide bond. By directly attaching PTX to MSN, we can significantly enhance the PTX´s loading degree and achieve the optimum drug loading ratio to DOX, therefore, to generate the best synergistical effect. More importantly, PTX and the linker act as a redox-sensitive “gate” to precisely control the release profile of DOX and PTX. Subsequently, polystyrene sulfonate (PSS) is electrostatically coated to DOX loaded MSN-PTX in microfluidics to achieve acidic pH responsive, because free amino group on MSN surface has protonation state at acidic pH and the electrostatic interaction will be destroyed at pH 5. In addition, PSS can also neutralize the surface zeta potential, thus reduce the non-specific endocytosis of healthy cells. By evaluating cell vi...