Fukushima Daichi, Sk Ugir Hossain, Sakamoto Yasuhiro, Nakase Ikuhiko, Kojima Chie
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan.
Colloids Surf B Biointerfaces. 2015 Aug 1;132:155-60. doi: 10.1016/j.colsurfb.2015.05.012. Epub 2015 May 14.
Dendrimers are synthetic macromolecules with unique structures that can work as nanoplatforms for both photothermogenic gold nanoparticles (AuNPs) and thermosensitive elastin-like peptides (ELPs) with valine-proline-glycine-valine-glycine (VPGVG) repeats. In this study, photothermogenic AuNPs were loaded into thermo-responsive elastin-mimetic dendrimers (dendrimers conjugating ELPs at their periphery) to produce dual stimuli-sensitive nanoparticles. Polyamidoamine G4 dendrimers were modified with acetylated VPGVG and (VPGVG)2, and the resulting materials were named ELP1-den and ELP2-den, respectively. The AuNPs were prepared by the reduction of Au ions using a dendrimer-nanotemplated method. The AuNP-loaded elastin-mimetic dendrimers exhibited photothermal properties. ELP1-den and ELP2-den showed similar temperature-dependent changes in their conformations. Phase transitions were observed at around 55°C and 35°C for the AuNP-loaded ELP1-den and AuNP-loaded ELP2-den, respectively, but not for the corresponding PEGylated dendrimer. In contrast to the AuNP-loaded PEGylated dendrimer, AuNP-loaded ELP2-den readily associated with cells and induced efficient photocytotoxicity at 37°C. The cell association and the photocytotoxicity properties of AuNP-loaded ELP2-den could be controlled by temperature. These results therefore suggest that dual stimuli-sensitive dendrimer nanoparticles of this type could be used for photothermal therapy.
树枝状大分子是具有独特结构的合成大分子,可作为用于光热金纳米颗粒(AuNP)和具有缬氨酸-脯氨酸-甘氨酸-缬氨酸-甘氨酸(VPGVG)重复序列的热敏弹性蛋白样肽(ELP)的纳米平台。在本研究中,将光热AuNP加载到热响应性弹性蛋白模拟树枝状大分子(在其外围共轭ELP的树枝状大分子)中,以制备双刺激敏感纳米颗粒。用乙酰化的VPGVG和(VPGVG)2修饰聚酰胺胺G4树枝状大分子,所得材料分别命名为ELP1-den和ELP2-den。通过使用树枝状大分子纳米模板法还原金离子来制备AuNP。负载AuNP的弹性蛋白模拟树枝状大分子表现出光热性质。ELP1-den和ELP2-den在构象上表现出相似的温度依赖性变化。对于负载AuNP的ELP1-den和负载AuNP的ELP2-den,分别在约55°C和35°C观察到相变,但相应的聚乙二醇化树枝状大分子未观察到相变。与负载AuNP的聚乙二醇化树枝状大分子相比,负载AuNP的ELP2-den在37°C时容易与细胞结合并诱导有效的光细胞毒性。负载AuNP的ELP2-den的细胞结合和光细胞毒性特性可通过温度控制。因此,这些结果表明这种类型的双刺激敏感树枝状大分子纳米颗粒可用于光热疗法。