Abstract
A pH/redox-triggered mesoporous silica nanoparticle (MSN)-based nanoplatform has been fabricated for doxorubicin/paclitaxel (DOX/PTX) codelivery. 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 PTX́s 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, polystyrenesulfonate (PSS) is electrostatically coated to DOX loaded MSN-PTX in microfluidics to achieve acidic pH responsive, because the free amino group on MSN surface has a 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 nonspecific endocytosis of healthy cells. By evaluating cell viability in cancer cell BT549 and healthy breast cell MCF-10A, we observed that the nanoparticles can selectively release DOX and PTX and eliminate cancer cells, while they will have negligible effect on the healthy breast cells, due to the acidic and redox microenvironment in cancer cells. Overall, we have developed a nanoplatform for precise DOX/PTX combination therapy with high selectivity between cancer cells and healthy cells.
Highlights
During the past decades, the incidence and mortality of cancer is continually increasing, posing challenges for the current medication.[1,2] Nowadays, the main clinical cancer treatments include surgery, radiotherapy, and chemotherapy.[3,4] Among them, chemotherapy is the most accessible therapeutic option for tumors
The dithiodipropionic acid (DTDP) is converted to dithiodipropionic anhydride (DTDPA), it is conjugated with PTX
DOX was directly loaded in the pores of mesoporous silica nanoparticle (MSN), whereas PTX was conjugated to MSN through three steps of chemical reactions, via a linker with a disulfide bond, could control the DOX and PTX release by redox responsive
Summary
The incidence and mortality of cancer is continually increasing, posing challenges for the current medication.[1,2] Nowadays, the main clinical cancer treatments include surgery, radiotherapy, and chemotherapy.[3,4] Among them, chemotherapy is the most accessible therapeutic option for tumors. To prevent the PTXs direct expose to physiological environment and further increase the tumor specificity of nanoparticles, PSS is coated on top of DOX loaded MSN-PTX via microfluidics, which has been widely used for nanoparticle fabrication and nanocomponents related drug loading and delivery.[30−32] Basically, microfluidics technology can be used to process very small quantities of samples, and the size, shape and functional surface of the fabricated nanoparticles can be tuned. These advantages can facilitate drug delivery and control the release profiles. The effects and selectivity of this nanoparticle between cancer cells and healthy cells are evaluated with breast cancer cell BT549 and healthy breast cell MCF-10
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