RT Journal Article T1 Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics A1 Villar Álvarez, Eva María A1 Cambón Freire, Adriana A1 Pardo Montero, Alberto A1 Mosquera Rodríguez, Víctor A1 Bouzas Mosquera, Alberto A1 Topete Camacho, Antonio A1 Barbosa Fernández, Silvia A1 Taboada Antelo, Pablo A1 Mosquera Tallón, Víctor K1 Drug release K1 Layers K1 Nanoparticles K1 Cells K1 Irradiation AB In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy PB American Chemical Society SN 2470-1343 YR 2018 FD 2018 LK http://hdl.handle.net/10347/22053 UL http://hdl.handle.net/10347/22053 LA eng NO Villar-Alvarez, E., Cambón, A., Pardo, A., Mosquera, V., Bouzas-Mosquera, A., Topete, A., Barbosa, S., Taboada, P. and Mosquera, V., 2018. Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics. ACS Omega, 3(10), pp.12633-12647 NO Authors thank AIE for funding through Project MAT2016-80266-R. FEDER funds are also greatly acknowledged. E.V.A. and A.P. are grateful to the Spanish Ministerio de Economia y Competitividad for their FPU fellowships DS Minerva RD 29 abr 2026