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@mSiO2) 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@mSiO2/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@mSiO2/DOX notably enhances the cell killing effect through induction of cell apoptosis. In addition, Se@Au@mSiO2/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.
Highlights
Cancer is a worldwide problem with high rates of morbidity and mortality[1]
Synthesis and characterization of Se@Au@mSiO2/DOX a novel nanoplatform was designed by assembling nano-Se on the surface of NIR-responsive Au@mSiO2/DOX nanoparticles for the effective treatment of metastatic breast cancer (Se@Au@mSiO2/DOX, Fig. 1)
During NIR irradiation, the surface plasmon resonance (SPR) property of the AuNR would act as a localized heat source and exhibit a photothermal effect
Summary
Cancer is a worldwide problem with high rates of morbidity and mortality[1]. The clinical application of numerous broad-spectrum chemotherapeutic drugs has been hindered owing to severe toxicity at high doses to vital organs, including the liver, kidney, spleen, and lungs and immune system and ineffectiveness at low doses[2,3].To improve the anticancer effects and overcome the side-effects, multiple anticancer agents or small molecules can be co-administered. Cancer is a worldwide problem with high rates of morbidity and mortality[1]. The clinical application of numerous broad-spectrum chemotherapeutic drugs has been hindered owing to severe toxicity at high doses to vital organs, including the liver, kidney, spleen, and lungs and immune system and ineffectiveness at low doses[2,3]. It has been difficult to integrate two drugs with different physicochemical characteristics onto a single carrier, and it has proven a tedious task to manipulate the ratiometric release of encapsulated compounds[5]. Given these setbacks, alternative strategies need to be employed to enhance therapeutic selectivity and reduce chemotherapeutic drug toxicity
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