College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou, Fujian, China.
Sci Rep. 2013;3:1293. doi: 10.1038/srep01293.
Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action.
纳米技术在药物输送方面得到了广泛的探索。在这里，我们介绍了一种基于纳米药物协同光热激活物理和生物效应的概念，该纳米药物结合了纳米颗粒-药物偶联物。为了验证这一概念，我们利用肿瘤坏死因子-α包覆的金纳米球（Au-TNF）在激光脉冲下加热。为了提高组织透明近红外窗口中的光热效率，我们探索了稍微椭圆形的纳米颗粒、其聚集以及激光诱导的非线性动态现象，导致光热和光声共振的放大和光谱锐化，相对于线性等离子体共振发生红移。使用一种小鼠癌模型，我们证明了与激光、Au-TNF 单独或激光与无 TNF 的金纳米球相比，Au-TNF 缀合物的治疗效果更高。低毒的 Au-TNF 缀合物的光热激活，该缀合物目前正在人体进行 II 期临床试验，并且激光已获得医疗应用批准，为开发具有协同抗肿瘤治疗作用的临床相关纳米药物开辟了新途径。
