RT Journal Article
T1 Inhibiting HER3 Hyperphosphorylation in HER2‐Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells
A1 Villar-Álvarez, Eva
A1 Golán‐Cancela, Irene
A1 Pardo Montero, Alberto
A1 Velasco Rodríguez, Brenda
A1 Fernández‐Vega, Javier
A1 Cambón Freire, Adriana
A1 Al‐Modlej, Abeer
A1 Topete Camacho, Antonio
A1 Barbosa Fernández, Silvia
A1 Costoya Puente, José Antonio
A1 Taboada Antelo, Pablo
K1 HER3 Hyperphosphorylation
K1 Breast cancer
K1 Receptor 3
K1 Oncoproteins
K1 Therapy
AB Treatment 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 proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier
PB Wiley
SN 1613-6810
YR 2023
FD 2023-08-26
LK http://hdl.handle.net/10347/31270
UL http://hdl.handle.net/10347/31270
LA eng
NO Small 2023, 2303934
NO E.V.-A. and I.G.-C. contributed equally to this work. This work was sup ported by the Agencia Estatal de Investigación (AEI) through ProjectNo. PID2019-109517RB-I00) and from the Xunta de Galicia, Project No.ED431C2022/18. European Regional Development Funds are also ac knowledged. A.A.-M. and P.T. also thank the International Scientific Part nership Program ISSP at King Saud University for additional funding ofthis research through Grant No. ISPP-144. This work also received fi nancial support from the ISCIII, Ministerio de Economía y Competitivi dad (Grant No. PI15/01129; J.A.C.), and the AEI (Grant No. PID2020-113501RB-I00; J.A.C.). I.-G.C. thanks for financial support through GrantNo. PRE/2011/131, and the Centro Singular de Investigación de Galiciaaccreditation Grant No. 2016–2019 ED431G/05)
DS Minerva
RD 23 abr 2026