Inhibiting HER3 Hyperphosphorylation in HER2 ‐Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells

A multimodal theranostic nanoplatform to treat breast cancer overexpressing the human epidermal growth factor receptors 2 (HER2) and 3 (HER3) is developed, and consisting of doxorubicin-loaded branched gold nanoshells functionalized with a small interfering RNA against HER3 and the HER2-specific antibody Trastuzumab able to simultaneously combine chemo- and photothermal, RNA silencing and immuno-therapies overcoming chemoresistance and reducing tumor size in vivo. AbstractTreatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal  theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+/HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferat...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research