Department of Chemical & Materials Engineering, University of Kentucky, Lexington, KY 40506-0046, USA.
J Biomater Sci Polym Ed. 2013;24(9):1112-26. doi: 10.1080/09205063.2012.741321. Epub 2012 Nov 20.
Hyperthermia, the heating of tissue from 41 to 45 °C, has been shown to improve the efficacy of cancer therapy when used in conjunction with irradiation and/or chemotherapy. In this work, hydrogel nanocomposites have been developed that can control the delivery of both heat and a chemotherapeutic agent (e.g. paclitaxel). The nanocomposites studied involve a stealth, poly(ethylene glycol) (PEG)-based system comprised of PEG (n = 1000) methyl ether methacrylate and PEG (n = 400) dimethacrylate with iron oxide nanoparticles physically entrapped within the hydrogel matrices. The capability of the hydrogel nanocomposites to be heated in an alternating magnetic field was demonstrated. The heating of the hydrogel systems was dependent on the crosslinking of the hydrogel network where hydrogels with lower swelling ratios were found to heat to a greater extent than those with higher ratios. In addition, paclitaxel was shown to exhibit non-Fickian release from the hydrogel systems, with the amount of drug released dependent on the hydrogel network structure. Three cell lines: M059K (glioblastoma), MDA MB 231 (breast carcinoma), and A549 (lung adenocarcinoma) were exposed to paclitaxel only, hyperthermia only, and both paclitaxel and hyperthermia to determine if a synergistic cytotoxic effect was possible for these cell lines. The efficacy of paclitaxel was greater with hyperthermia for the A549 cells; however, the M059K and MDA MB 231 did not show the same response.
热疗,即把组织加热到 41 到 45°C,已被证明在与放疗和/或化疗联合使用时可以提高癌症治疗的效果。在这项工作中,开发了水凝胶纳米复合材料,它可以控制热和化疗药物(如紫杉醇)的递送。所研究的纳米复合材料涉及一种隐形、基于聚(乙二醇)(PEG)的系统,由聚乙二醇(n=1000)甲基醚甲基丙烯酸酯和聚乙二醇(n=400)二甲基丙烯酸酯组成,氧化铁纳米粒子物理地嵌入水凝胶基质中。证明了水凝胶纳米复合材料在交变磁场中加热的能力。水凝胶系统的加热取决于水凝胶网络的交联,其中发现具有较低溶胀比的水凝胶加热到更大程度比那些具有更高比率的水凝胶。此外,紫杉醇从水凝胶系统中表现出非菲克扩散释放,释放的药物量取决于水凝胶网络结构。将三种细胞系:M059K(神经胶质瘤)、MDA MB 231(乳腺癌)和 A549(肺腺癌)仅暴露于紫杉醇、仅热疗以及紫杉醇和热疗两者下,以确定这些细胞系是否存在协同细胞毒性作用。对于 A549 细胞,紫杉醇与热疗联合使用的效果更好;然而,M059K 和 MDA MB 231 并没有表现出相同的反应。