Influence of hyperthermia on efficacy and uptake of carbon nanohorn-cisplatin conjugates.
Influence of hyperthermia on efficacy and uptake of carbon nanohorn-cisplatin conjugates.
复制标题
DOI：
10.1115/1.4026318
复制
发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Matthew R. DeWitt;Allison M Pekkanen-;J. Robertson;Christopher G. Rylander;M. Nichole Rylander
中科院分区：
文献类型：
--
作者：
Matthew R. DeWitt;Allison M Pekkanen-;J. Robertson;Christopher G. Rylander;M. Nichole Rylander
单壁碳纳米角（SWNHs）由于其吸收近红外光和沉积热量的能力，在光热治疗中具有重要的应用潜力。此外，它们广泛的相对表面积和体积使它们成为理想的药物输送载体。设想了一种新的多模态治疗方法，其中激光激发可以与化疗- swnh偶联物联合使用，以热增强运输药物的治疗功效。虽然轻度热疗（41-43°C）已被证明可以增加顺铂（CDDP）等药物的细胞摄取，导致热增强，但目前关于热疗对装载顺铂的纳米颗粒的影响的研究有限。在使用碳二亚胺化学反应将CDDP附着在SWNHs的外表面，并使用硝酸将CDDP掺入内部体积后，我们确定了亚热对CDDP- swnh偶联物疗效的影响。将大鼠膀胱移行癌细胞暴露于游离CDDP或两种CDDP- swnh偶联物中的一种体外37℃和42℃，每种处理的最大抑制浓度（IC50）为一半。体外实验结果表明，与游离CDDP不同，CDDP- swnh偶联物在42°C时不表现出热增强。当细胞暴露在42度时，与37度相比，表面附着和体积负载的CDDP-SWNH偶联物分别增加了16%和7%的活力。与37°C相比，42°C时CDDP-SWNH偶联物的摄取减少，这揭示了纳米颗粒摄取对CDDP-SWNH偶联物疗效的重要性，特别是当热疗用作佐剂时，并证明了颗粒大小在温和热疗期间对摄取的影响。摄取和药物释放研究阐明了在不同温度下药效研究中所见的活力差异。我们推测，与药物SWNH偶联物相比，游离药物的热增强功效差异是由于它们的内在尺寸差异，因此它们的细胞摄取模式是扩散或内吞作用。这些实验表明，调整纳米颗粒-药物偶联物的性质对于最大化细胞摄取以确保纳米颗粒介导的光热化疗治疗中的热增强具有重要意义。
Single-walled carbon nanohorns (SWNHs) have significant potential for use in photothermal therapies due to their capability to absorb near infrared light and deposit heat. Additionally, their extensive relative surface area and volume makes them ideal drug delivery vehicles. Novel multimodal treatments are envisioned in which laser excitation can be utilized in combination with chemotherapeutic-SWNH conjugates to thermally enhance the therapeutic efficacy of the transported drug. Although mild hyperthermia (41-43 °C) has been shown to increase cellular uptake of drugs such as cisplatin (CDDP) leading to thermal enhancement, studies on the effects of hyperthermia on cisplatin loaded nanoparticles are currently limited. After using a carbodiimide chemical reaction to attach CDDP to the exterior surface of SWNHs and nitric acid to incorporate CDDP in the interior volume, we determined the effects of mild hyperthermia on the efficacy of the CDDP-SWNH conjugates. Rat bladder transitional carcinoma cells were exposed to free CDDP or one of two CDDP-SWNH conjugates in vitro at 37 °C and 42 °C with the half maximal inhibitory concentration (IC50) for each treatment. The in vitro results demonstrate that unlike free CDDP, CDDP-SWNH conjugates do not exhibit thermal enhancement at 42 °C. An increase in viability of 16% and 7% was measured when cells were exposed at 42 deg compared to 37 deg for the surface attached and volume loaded CDDP-SWNH conjugates, respectively. Flow cytometry and confocal microscopy showed a decreased uptake of CDDP-SWNH conjugates at 42 °C compared to 37 °C, revealing the importance of nanoparticle uptake on the CDDP-SWNH conjugate's efficacy, particularly when hyperthermia is used as an adjuvant, and demonstrates the effect of particle size on uptake during mild hyperthermia. The uptake and drug release studies elucidated the difference in viability seen in the drug efficacy studies at different temperatures. We speculate that the disparity in thermal enhancement efficacy observed for free drug compared to the drug SWNH conjugates is due to their intrinsic size differences and, therefore, their mode of cellular uptake: diffusion or endocytosis. These experiments indicate the importance of tuning properties of nanoparticle-drug conjugates to maximize cellular uptake to ensure thermal enhancement in nanoparticle mediated photothermal-chemotherapy treatments.