School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University , Seoul 06351, Republic of Korea.
ACS Nano. 2016 Dec 27;10(12):10858-10868. doi: 10.1021/acsnano.6b05113. Epub 2016 Nov 16.
Optically active nanomaterials have shown great promise as a nanomedicine platform for photothermal or photodynamic cancer therapies. Herein, we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA) for photothermally boosted photodynamic tumor ablation. Unlike other supramolecular gold constructs based on gold nanoparticle building blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan conjugates as a drug carrier for a hydrophobic photodynamic therapy agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold upon which gold can grow. Gold nanoclusters were selectively installed on the outer shell of the hyaluronan nanoassembly, forming a gold shell. Given the dual protection effect by the hyaluronan self-assembly as well as by the inorganic gold shell, verteporfin-encapsulated GNc-HyNA (Vp-GNc-HyNA) exhibited outstanding stability in the bloodstream. Interestingly, the fluorescence and photodynamic properties of Vp-GNc-HyNA were considerably quenched due to the gold nanoclusters covering the surface of the nanoassemblies; however, photothermal activation by 808 nm laser irradiation induced a significant increase in temperature, which empowered the PDT effect of Vp-GNc-HyNA. Furthermore, fluorescence and photodynamic effects were recovered far more rapidly in cancer cells due to certain intracellular enzymes, particularly hyaluronidases and glutathione. Vp-GNc-HyNA exerted a great potential to treat tumors both in vitro and in vivo. Tumors were completely ablated with a 100% survival rate and complete skin regeneration over the 50 days following Vp-GNc-HyNA treatment in an orthotopic breast tumor model. Our results suggest that photothermally boosted photodynamic therapy using Vp-GNc-HyNA can offer a potent therapeutic means to eradicate tumors.
具有手性的纳米材料在光热或光动力癌症治疗的纳米医学平台方面显示出巨大的应用潜力。在此，我们报告了一种基于金纳米簇-透明质酸纳米组装体（GNc-HyNA）的用于光热增强光动力肿瘤消融的纳米载体。与其他基于金纳米颗粒构建块的超分子金结构不同，该系统利用两亲性透明质酸缀合物的纳米组装作为疏水性光动力治疗剂维替泊芬、聚合物还原剂和有机纳米支架的药物载体，金可以在其上生长。金纳米簇被选择性地安装在透明质酸纳米组装体的外壳上，形成金壳。由于透明质酸自组装以及无机金壳的双重保护作用，包载维替泊芬的 GNc-HyNA（Vp-GNc-HyNA）在血液中表现出优异的稳定性。有趣的是，由于金纳米簇覆盖了纳米组装体的表面，Vp-GNc-HyNA 的荧光和光动力性质被显著猝灭；然而，808nm 激光照射的光热激活导致温度显著升高，从而增强了 Vp-GNc-HyNA 的 PDT 效应。此外，由于某些细胞内酶，特别是透明质酸酶和谷胱甘肽，Vp-GNc-HyNA 在癌细胞中的荧光和光动力效应恢复得更快。Vp-GNc-HyNA 在体外和体内均显示出治疗肿瘤的巨大潜力。在原位乳腺癌模型中，Vp-GNc-HyNA 治疗后 50 天内，肿瘤完全消融，存活率为 100%，皮肤完全再生。我们的结果表明，使用 Vp-GNc-HyNA 的光热增强光动力疗法可以为消除肿瘤提供一种有效的治疗手段。
