title: Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation.
abstract: Optically active nanomaterials have shown great promise as a nanomedicine platform for photothermal or photodynamic cancer therapies. Herein, we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA) for photothermally boosted photodynamic tumor ablation. Unlike other supramolecular gold constructs based on gold nanoparticle building blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan conjugates as a drug carrier for a hydrophobic photodynamic therapy agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold upon which gold can grow. Gold nanoclusters were selectively installed on the outer shell of the hyaluronan nanoassembly, forming a gold shell. Given the dual protection effect by the hyaluronan self-assembly as well as by the inorganic gold shell, verteporfin-encapsulated GNc-HyNA (Vp-GNc-HyNA) exhibited outstanding stability in the bloodstream. Interestingly, the fluorescence and photodynamic properties of Vp-GNc-HyNA were considerably quenched due to the gold nanoclusters covering the surface of the nanoassemblies; however, photothermal activation by 808 nm laser irradiation induced a significant increase in temperature, which empowered the PDT effect of Vp-GNc-HyNA. Furthermore, fluorescence and photodynamic effects were recovered far more rapidly in cancer cells due to certain intracellular enzymes, particularly hyaluronidases and glutathione. Vp-GNc-HyNA exerted a great potential to treat tumors both in vitro and in vivo. Tumors were completely ablated with a 100% survival rate and complete skin regeneration over the 50 days following Vp-GNc-HyNA treatment in an orthotopic breast tumor model. Our results suggest that photothermally boosted photodynamic therapy using Vp-GNc-HyNA can offer a potent therapeutic means to eradicate tumors.
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Hwa Seung
authors.initials: HS
authors.lastname: Han
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Hansang
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Minchang
authors.initials: M
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: An
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Sol
authors.initials: S
authors.lastname: Shin
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Seunglee
authors.initials: S
authors.lastname: Kwon
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Doo Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University , Seoul 06351, Republic of Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D004337:Drug Carriers; D006046:Gold; D006801:Humans; D006820:Hyaluronic Acid; D053768:Metal Nanoparticles; D009369:Neoplasms / Q000628:therapy; D010778:Photochemotherapy
chemical_list: D004337:Drug Carriers; D006046:Gold; D006820:Hyaluronic Acid
keywords: gold; hyaluronan; hybrid nanomaterials; photodynamic therapy; photothermal therapy