title: Fluorescent drug-loaded, polymeric-based, branched gold nanoshells for localized multimodal therapy and imaging of tumoral cells.
abstract: Here we report the synthesis of PLGA/DOXO-core Au-branched shell nanostructures (BGNSHs) functionalized with a human serum albumin/indocyanine green/folic acid complex (HSA-ICG-FA) to configure a multifunctional nanotheranostic platform. First, branched gold nanoshells (BGNSHs) were obtained through a seeded-growth surfactant-less method. These BGNSHs were loaded during the synthetic process with the chemotherapeutic drug doxorubicin, a DNA intercalating agent and topoisomerase II inhibitior. In parallel, the fluorescent near-infrared (NIR) dye indocyanine green (ICG) was conjugated to the protein human serum albumin (HSA) by electrostatic and hydrophobic interactions. Subsequently, folic acid was covalently attached to the HSA-ICG complex. In this way, we created a protein complex with targeting specificity and fluorescent imaging capability. The resulting HSA-ICG-FA complex was adsorbed to the gold nanostructures surface (BGNSH-HSA-ICG-FA) in a straightforward incubation process thanks to the high affinity of HSA to gold surface. In this manner, BGNSH-HSA-ICG-FA platforms were featured with multifunctional abilities: the possibility of fluorescence imaging for diagnosis and therapy monitoring by exploiting the inherent fluorescence of the dye, and a multimodal therapy approach consisting of the simultaneous combination of chemotherapy, provided by the loaded drug, and the potential cytotoxic effect of photodynamic and photothermal therapies provided by the dye and the gold nanolayer of the hybrid structure, respectively, upon NIR light irradiation of suitable wavelength. The combination of this trimodal approach was observed to exert a synergistic effect on the cytotoxicity of tumoral cells in vitro. Furthermore, FA was proved to enhance the internalization of nanoplatform. The ability of the nanoplatforms as fluorescence imaging contrast agents was tested by preliminary analyzing their biodistribution in vivo in a tumor-bearing mice model.
authors.affiliation: Grupo de Física de Coloides y Polímeros, Departamento de Física de la Materia Condensada, Universidad de Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Topete
authors.forename: Manuel
authors.initials: M
authors.lastname: Alatorre-Meda
authors.forename: Pablo
authors.initials: P
authors.lastname: Iglesias
authors.forename: Eva M
authors.initials: EM
authors.lastname: Villar-Alvarez
authors.forename: Silvia
authors.initials: S
authors.lastname: Barbosa
authors.forename: José A
authors.initials: JA
authors.lastname: Costoya
authors.forename: Pablo
authors.initials: P
authors.lastname: Taboada
authors.forename: Víctor
authors.initials: V
authors.lastname: Mosquera
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005456:Fluorescent Dyes / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D057145:Nanoshells / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D012709:Serum Albumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006046:Gold; D004317:Doxorubicin