Liang Zhongshi, Li Xingui, Xie Yegui, Liu Shunying
Institute for Advanced Interdisciplinary Research, East China Normal University, 200062 Shanghai, People's Republic of China.
Biomed Mater. 2014 Apr;9(2):025012. doi: 10.1088/1748-6041/9/2/025012. Epub 2014 Feb 13.
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.
在体内循环的纳米材料在疾病诊断和治疗方面具有巨大潜力。在此，我们报道“智能”金纳米壳能够携带药物负载，并且其固有的近红外（NIR）等离子体共振能够实现化疗和热疗的联合应用。“智能”金纳米壳（命名为DOX/A54@GNs）由以下部分组成：（a）具有近红外等离子体共振的金纳米壳（GNs），其不仅作为纳米块，还能产生局部热量以实现热疗；（b）抗癌药物阿霉素（DOX），通过pH依赖性可生物降解共聚物硫醇聚（乙二醇）衍生物经氨基甲酸酯键连接到纳米块上；（c）靶向肽A54（AGKGTPSLETTP），以促进其靶向肝癌细胞并增强细胞摄取。与在中性环境（pH 7.4）中相比，共轭的DOX在酸性环境（pH 5.3）中从DOX/A54@GNs释放得更快，这是细胞内肿瘤药物释放所需的特性。DOX修饰的GNs表现出pH依赖性释放行为，使用电感耦合等离子体原子发射光谱法（ICP - AES）和显微镜进行的体外细胞摄取实验表明，在人肝癌细胞系BEL - 7402中，A54修饰的GNs比未修饰A54的GNs具有更高的内化率。进行了流式细胞术和荧光镜分析，以揭示在联合化疗和热疗下A54修饰的GNs引起的细胞凋亡增强。这些结果表明，DOX/A54@GNs可作为具有pH触发药物释放特性的多功能纳米材料系统，用于肿瘤靶向化疗和热疗。
