Study On Redox-responsive Cytochrome C End-capped Mesoporous Silica Nanoparticles For Tumor-targeted Triplex Therapy

Mesoporous silica nanoparticles (MSNs) present themselves superior advantagesto other vehicles for drug delivery, due to their unique features, such as high loadingcapacity for carrying either hydrophilic or hydrophobic drugs, tunable mesopores sizesfor different guest molecules, and abundant silanol groups for further chemicalfunctionalization.To develop carriers for efficient anti-cancer drug delivery with reduced side effects, abiocompatible and redox-responsive nanocontainer based on mesoporous silicananoparticles (MSNs) for tumor-targeted triplex therapy is reported in this study. Thenanocontainer is fabricated by immobilizing cytochrome c (CytC) onto the MSNs assealing agent via intermediate linkers of disulfide bonds for redox-responsiveintracellular drug delivery. Moreover, AS1411aptamer is further tailored onto thenanocontainer for cell/tumor targeting. The successful construction of redox-responsivenanocontainer is confirmed by BET/BJH analysis, transmission electron microscopy,Fourier transform infrared spectroscopy, and fluorescence spectroscopy and thermogravimetric analysis, respectively. Detailed investigations demonstrate that anticancerdrug of doxorubicin (DOX) loaded nanocontainers could be triggered by reductant (e. g.glutathione) within cellular microenvironment and release DOX to induce tumor cellapoptosis in vitro. More importantly, the nanocontainer displays great potential fortumor targeting and achieves triplex therapy effects on the tumor growth inhibition invivo through the payloading drug of DOX, gatekeeper of CytC and targeting componentof AS1411aptamer, which are reflected by the change of tumor size, TUNEL stainingand HE staining assays. This study affords an alternative for the development ofmulti-model nanotherapeutics for efficient cancer therapy.