Ariyasu Shinya, Mu Jing, Zhang Xiao, Huang Ying, Yeow Edwin Kok Lee, Zhang Hua, Xing Bengang
Division of Chemistry & Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, Singapore, 637371, Singapore.
Center for Programmable Materials, School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue, Singapore 639798, Singapore.
Bioconjug Chem. 2017 Apr 19;28(4):1059-1067. doi: 10.1021/acs.bioconjchem.6b00741. Epub 2017 Mar 8.
In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce localized heat for targeted ablation of cancer cells. Among the various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially molybdenum disulfide (MoS), have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability. In line with the great potential of MoS-based nanomaterials in biomedical applications, their intrinsic therapeutic performance and corresponding cellular response are required to be continually investigated. In order to further improve MoS-based PTT efficacy and dissect the molecular mechanism during heat stimuli, in this study, we successfully designed a novel and effective PTT platform by integration of MoS nanosheets with peptide-based inhibition molecules to block the function of heat shock proteins (Hsp90), one type of chaperone proteins that play protective roles in living systems against cellular photothermal response. Such a combined nanosystem could effectively induce cell ablation and viability assays indicated approximately 5-fold higher PTT treatment efficacy (8.8% viability) than that of MoS itself (48% viability) upon 808 nm light irradiation. Moreover, different from the case based on MoS alone that could cause tumor ablation through the process of necrosis, the detailed mechanism analysis revealed that the inhibition of Hsp90 could significantly increase the photothermally mediated apoptosis, hence resulting in remarkable enhancement of photothermal treatment. Such promising studies provide the great opportunity to better understand the cellular basis of light-triggered thermal response. Moreover, they can also facilitate the rational design of new generations of PTT platforms toward future theranostics.
与传统的肿瘤治疗方法相比，光热疗法（PTT）是一种创新的治疗策略，它利用光产生局部热量以靶向消融癌细胞。在各种产热纳米材料中，过渡金属二硫化物纳米片，尤其是二硫化钼（MoS），由于其在近红外（NIR）组织透明窗口中的强吸收能力和出色的光热转换能力，最近被作为有前景的PTT候选材料之一进行研究。鉴于基于MoS的纳米材料在生物医学应用中的巨大潜力，需要不断研究它们的内在治疗性能和相应的细胞反应。为了进一步提高基于MoS的PTT疗效并剖析热刺激过程中的分子机制，在本研究中，我们通过将MoS纳米片与基于肽的抑制分子整合，成功设计了一种新型有效的PTT平台，以阻断热休克蛋白（Hsp90）的功能，热休克蛋白是一类伴侣蛋白，在生物系统中对细胞光热反应起保护作用。这种组合纳米系统能有效诱导细胞消融，活力测定表明，在808 nm光照射下，PTT治疗效果比MoS本身（活力为48%）高出约5倍（活力为8.8%）。此外，与仅基于MoS通过坏死过程导致肿瘤消融的情况不同，详细的机制分析表明，抑制Hsp90可显著增加光热介导的细胞凋亡，从而显著增强光热治疗效果。这些有前景的研究为更好地理解光触发热反应的细胞基础提供了绝佳机会。此外，它们还可以促进面向未来治疗诊断学的新一代PTT平台的合理设计。
