JANG ET AL. VOL. 8 ’ NO. 1 ’ 467 –475 ’ 2014 www.acsnano.org 467 January 02, 2014 C 2014 American Chemical Society Facile Synthesis and Intraparticle Self- Catalytic Oxidation of Dextran-Coated Hollow AuÀAg Nanoshell and Its Application for Chemo-Thermotherapy Hongje Jang, Young-Kwan Kim, Hyun Huh, and Dal-Hee Min * Center for RNA Research, Institute for Basic Science, Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea H ollow gold nanostructures have been extensively investigated for applications in biosensing, 1,2 imag- ing, 3,4 catalysis, 5,6 and hyperthermia 7À9 due to their unique physicochemical properties including reduced density with nanoscale size, interior vacancy, high surface-to- volume ratio, strong surface plasmon resonance (SPR), 10À13 and photothermal effect. 14,15 Among them, photothermal effect is attrac- tive for therapeutic applications such as a cancer treatment modality by inducing hy- perthermia. A strong plasmon absorption band in the near-infrared (NIR) wavelength of hollow gold nanostructures can induce direct damage to the cells treated with the nanostructures by hyperthermia. 16À18 NIR irradiation is ideal for in vivo photothermal applications due to its low absorption by tissue chromophores including hemoglo- bin, thus allowing deep tissue penetration. 19À21 One approach for cancer therapy combines modalities of hyperthermia and chemother- apy, so-called chemo-thermotherapy, in which hyperthermia is used at a sublethal level to potentiate the therapeutic effect of anticancer agents. Another key feature of hollow gold nanostructures is catalytic ac- tivity which accelerates oxidative processes. First notable demonstration was reported on oxidation of CO to CO 2 by gold nanoclus- ters in 1989. 22 In principle, the high electric potential (E 0 = þ1.69 V) of gold provides high material stability against catalytic poi- soning against oxygen and other functional groups during the catalytic reaction. 23 Also, the high surface-to-volume ratio of gold nanomaterial ; even higher in hollow structures ; enables effective turnover rate in catalytic reactions. Selective oxidation prop- erty of gold nanomaterial in both gas and liquid phase can endow bulk-scale reaction with low activation energy, which is espe- cially useful for industrial application. 24 Oxi- dation of alcohols, 25À27 diols, 28 polyols, 29 and carbohydrates 30 by gold nanoclusters provides an opportunity for integrating the relevant chemical modification with the conjugation of biomolecules for various biological applications. Preparation of hollow gold nanostructures through galvanic replacement reaction was first reported by Xia and co-workers. 31 They employed galvanic replacement reaction which proceeds via oxidation of suspending silver nanostructures by AuCl 4 À ions due to the standard reduction potential difference (Ag þ |Ag pair: 0.7996 V vs SHE, AuCl 4 À |Au pair: 0.93 V vs SHE) in an aqueous solution. Unlike other hollow nanostructure formation * Address correspondence to dalheemin@snu.ac.kr. Received for review September 16, 2013 and accepted January 2, 2014. Published online 10.1021/nn404833b ABSTRACT Galvanic replacement reaction is a useful method to prepare various hollow nanostruc- tures. We developed fast and facile preparation of biocompatible and structurally robust hollow AuÀAg nanostructures by using dextran-coated Ag nanoparticles. Oxidation of the surface dextran alcohols was enabled by catalytic activity of the core AuÀAg nanostructure, introducing carbonyl groups that are useful for further bioconjugation. Subsequent doxorubicin (Dox) conjugation via Schiff base formation was achieved, giving high payload of approximately 35 000 Dox per particle. Near-infrared-mediated photothermal conversion showed high efficacy of the Dox- loaded AuÀAg nanoshell as a combinational chemo-thermotherapy to treat cancer cells. KEYWORDS: cancer . dextran . doxorubicin . hollow nanoparticle . photothermal therapy ARTICLE