Multimodal Selenium Nanoshell-capped Au@mSiO2 Nanoplatform for NIR-responsive Chemo-Photothermal Therapy against Metastatic Breast Cancer

Abstract

Multimodal therapeutic agents based on novel nanomaterials for multidrug resistance have attracted increasing attention in cancer therapy. In this study, we describe the construction of a programmed mesoporous silica-capped gold nanorod covered with nano-selenium overcoat (Se@Au@mSiO(2)) nanoparticles as a multifunctional nanoplatform to incorporate materials with specific chemotherapeutic, chemoprevention, and photoablation/hyperthermia functions that collectively contribute to enhance anticancer efficacy in multidrug-resistant breast cancer. The triple-combination-based nanosized Se@Au@mSiO(2)/DOX effectively accumulates in the tumor and the release of the therapeutic cargo could be remotely manipulated by mild near-infrared (NIR) irradiation. Se@Au@mSiO(2)/DOX notably enhances the cell killing effect through induction of cell apoptosis. In addition, Se@Au@mSiO(2)/DOX inhibits tumor cell growth through cell cycle arrest and induction of apoptosis via suppression of the Src/FAK/AKT signaling pathways. Synergistic Se-photothermal-chemotherapy combination exhibits significant tumor growth suppression and delayed tumor progression in vivo. Immunohistochemistry analysis shows elevated numbers of caspase-3 and PARP-immunolabeled cells and decreased Ki-67 + and CD31 + cancer cells in the tumor mass. No noticeable signs of organ damage or toxicity are observed after treatment with Se@Au@mSiO2/DOX (NIR+), which is further supported by hematology and biochemical analyses. Thus, Se@Au@mSiO2/DOX has potential for the clinical treatment of metastatic breast cancers with little or no adverse effects.