Yang Lingyan, Tseng Yu-Ting, Suo Guangli, Chen Liliang, Yu Jiantao, Chiu Wei-Jane, Huang Chih-Ching, Lin Chia-Hua
Key Laboratory of Nano-Bio Interface, Suzhou Key Laboratory for Nanotheranostics, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences , Suzhou 215123, China.
ACS Appl Mater Interfaces. 2015 Mar 11;7(9):5097-106. doi: 10.1021/am508117e. Epub 2015 Feb 27.
The objective of this study was to synthesize a nanocomposite, aptamer-gold nanoparticle-hybridized graphene oxide (Apt-AuNP-GO), to facilitate targeted treatment of tumor cells by near-infrared (NIR) light-activatable photothermal therapy. We also investigated whether Apt-AuNP-GO with NIR illumination modulates heat shock proteins (HSPs) expression leading to therapeutic response in human breast cancer cells. These findings can provide strategies for improving the photothermal therapy efficacy of cancer. The self-assembled Apt-AuNP-GO nanocomposite could selectively target MUC1-positive human breast cancer cells (MCF-7) due to the specific interaction between the MUC1-binding-aptamer and the MUC1 (type I transmembrane mucin glycoprotein) on cell membrane. In addition, Apt-AuNP-GO has a high light-to-heat conversion capability for photoabsorption of NIR light, and it is able to exert therapeutic effects on MCF-7 cells at an ultralow concentration without inducing adverse effects in healthy cells. The Apt-AuNP-GO nanocomposites combine the advantages of GOs, AuNPs, and Apts, possess specific targeting capability, excellent biocompatibility, and tumor cell destruction ability, suggesting great potential for application in the photothermal therapy of breast cancer. Under NIR illumination, Apt-AuNP-GO induced transient increase in HSP70 expression, which decreased thereafter. This phenomenon may cause irreversible damage to Apt-AuNP-GO-treated MCF-7 cell under NIR illumination. We also demonstrated that the combination therapy of heat and HSP70 inhibitor could synergistically generate marked tumoricidal effects against breast cancer. These results suggest that the degree and duration of HSP70 protein expression are correlated with therapeutic effects against breast cancer for Apt-AuNP-GO-assisted photothermal therapy. We believe that such a nanocomposite can be readily extended to the construction of HSP70 inhibitors-loaded Apt-AuNP-GO, which could deliver both heat and HSP70 inhibitors to tumorigenic regions for the chemo-photothermal therapy.
本研究的目的是合成一种纳米复合材料，即适配体-金纳米颗粒-杂化氧化石墨烯（Apt-AuNP-GO），以通过近红外（NIR）光激活光热疗法促进对肿瘤细胞的靶向治疗。我们还研究了经近红外照射的Apt-AuNP-GO是否会调节热休克蛋白（HSPs）的表达，从而在人乳腺癌细胞中产生治疗反应。这些发现可为提高癌症光热治疗疗效提供策略。自组装的Apt-AuNP-GO纳米复合材料可通过MUC1结合适配体与细胞膜上的MUC1（I型跨膜粘蛋白糖蛋白）之间的特异性相互作用，选择性地靶向MUC1阳性人乳腺癌细胞（MCF-7）。此外，Apt-AuNP-GO对近红外光具有高光热转换能力，能够在超低浓度下对MCF-7细胞发挥治疗作用，且不会对健康细胞产生不良影响。Apt-AuNP-GO纳米复合材料结合了氧化石墨烯、金纳米颗粒和适配体的优点，具有特异性靶向能力、优异的生物相容性和肿瘤细胞破坏能力，显示出在乳腺癌光热治疗中的巨大应用潜力。在近红外照射下，Apt-AuNP-GO诱导HSP70表达短暂增加，随后降低。这种现象可能会在近红外照射下对经Apt-AuNP-GO处理的MCF-7细胞造成不可逆损伤。我们还证明，热疗与HSP70抑制剂联合治疗可协同产生显著的杀瘤作用，对抗乳腺癌。这些结果表明，HSP70蛋白表达的程度和持续时间与Apt-AuNP-GO辅助光热治疗对乳腺癌的治疗效果相关。我们相信，这样的纳米复合材料可轻松扩展用于构建负载HSP70抑制剂的Apt-AuNP-GO，其可将热和HSP70抑制剂输送至肿瘤发生区域，用于化学光热治疗。
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