Chemo-photodynamic Co-therapy Based On Fe_3O4-Au@mSiO₂ Nanocomposites For Cancer Theranostics

It is well known that cancer is one of the most dangerous disease for human. It is imperative for us to take drastic measures to exploit a new therapeutic approach to cancer treatment. Many studies have been demonstrated combination treatment could be more effective to destroy cancer cells than simple treatment. Therefore, study to combine various treatments in nanoparticles for combination therapy and image is being considered as a promising way to cancer treatment.Herein, we developed a multifunctional Fe_3O4-Au@mSiO₂/PEM-based nanoparticles that combines five properties: magnetic targeting, high Dox/Ce6 loading,MR/CT dual-modal imaging, p H response, good biocompatibility. Then P-gp sh RNA was absorbed to Fe_3O4-Au@mSiO₂（Dox/Ce6）/PEM nanoparticles to form a drug/gene co-delivery nanocomposites. The mean particle size and zeta potential of the nanoparticles were 280 nm and +12.2 m V, respectively. Our data showed that Fe_3O4-Au@mSiO₂（Dox/Ce6）/PEM/P-gp sh RNA nanocomposites have synergistic tumor growth inhibition effect by CCK-8 and PI/Calcein-AM assays.In vivo experiments, the tumors of saline and nanoparticles groups grew rapidly. In contrast, a significant of tumor growth inhibited was observed in other groups. Effects were most pronounced in the group of Fe_3O4-Au@mSiO₂（Dox/Ce6）/PEM/P-gp sh RNA.The Fe_3O4-Au@mSiO₂（Dox/Ce6）/PEM/P-gp sh RNA group exhibited the smallest tumor weight, with their tumor growth inhibited by 88%. Accordingly, HE staining of tumor slices showed that while cells in untreated tumors largely retained their normal morphology, tumor cells in the combination treatment group were severely damaged.Notably, the therapeutic efficacy achieved in our combination therapy appeared to be obviously stronger than the simple treatment effect.These data highlight multifunctional Fe_3O4-Au@mSiO₂（Dox/Ce6）/PEM/P-gp sh RNA nanocomposites as an attractive platform of co-delivery of Dox, Ce6 and P-gp sh RNA for cancer combination treatment, and also making it a potential candidate for MR/CT imaging. It will provide a potent therapeutic choice in the cancer combination therapy.