title: 'Smart' gold nanoshells for combined cancer chemotherapy and hyperthermia.
abstract: Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that 'smart' gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The 'smart' gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia.
authors: Institute for Advanced Interdisciplinary Research, East China Normal University, 200062 Shanghai, People's Republic of China.
authors: Zhongshi
authors: Z
authors: Liang
authors: Xingui
authors: X
authors: Li
authors: Yegui
authors: Y
authors: Xie
authors: Shunying
authors: S
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D005471:Fluoroscopy; D006046:Gold / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced / Q000379:methods*; D053768:Metal Nanoparticles / Q000737:chemistry*; D057145:Nanoshells / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D010455:Peptides; D011108:Polymers; D011092:Polyethylene Glycols; D006046:Gold; D004317:Doxorubicin