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Near-infrared/pH dual-responsive nanocomplexes for targeted imaging and chemo/gene/photothermal tri-therapies of non-small cell lung cancer.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2020-03-07 , DOI: 10.1016/j.actbio.2020.03.004
Ziying Li 1 , Lisheng Zhu 1 , Weiqun Liu 1 , Yilin Zheng 1 , Xudong Li 1 , Jinxiang Ye 1 , Bifei Li 1 , Haijun Chen 2 , Yu Gao 1
Affiliation  

Combination therapy offers promising opportunities for treating advanced non-small cell lung cancer (NSCLC). Here, we established a chitosan-based nanocomplex CE7Q/CQ/S to deliver molecular-targeted drug erlotinib (Er), Survivin shRNA-expressing plasmid (SV), and photothermal agent heptamethine cyanine dye (Cy7) in one platform for simultaneous near-infrared (NIR) fluorescence imaging and triple-combination therapy of NSCLC bearing epidermal growth factor receptor (EGFR) mutations. The obtained CE7Q/CQ/S exhibited favorable photothermal effects, good DNA binding ability, and pH/NIR dual-responsive release behaviors. The conjugated Er could mediate specific delivery of Cy7 to EGFR-mutated NSCLC cells to enable targeted NIR fluorescence imaging and photothermal therapy (PTT). The in vitro and in vivo results showed that downregulation of Survivin expression and the photothermal effects could act synergistically with Er to induce satisfactory anticancer effects in either Er-sensitive or Er-resistant EGFR-mutated NSCLC cells. By integrating chemo/gene/photothermal therapies into one theranostic nanoplatform, CE7Q/CQ/S could significantly suppress EGFR-mutated NSCLC, indicating its potential use in treating NSCLC. STATEMENT OF SIGNIFICANCE: The development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved overall survival in patients with NSCLC driven by EGFR mutations. Unfortunately, the emergence of acquired resistance of EGFR-TKIs is almost inevitable after treatment. Here, we constructed a NIR/pH dual-responsive nanocomplex CE7Q/CQ/S based on chitosan which could integrate targeted near-infrared fluorescence imaging and chemo/gene/phototheramal tri-therapies together. We found that CE7Q/CQ/S possessed a promising outcome in fighting against EGFR-mutated NSCLC. The inhibition of Survivin expression and the application of photothermal therapy could act synergistically with erlotinib and reverse erlotinib resistance. The results of this work suggested that this chitosan-based combination therapeutic nanoplatform could be a promising candidate for NSCLC treatment.

中文翻译:

近红外/ pH双响应纳米复合物,用于非小细胞肺癌的靶向成像和化学/基因/光热三联疗法。

联合疗法为治疗晚期非小细胞肺癌(NSCLC)提供了有希望的机会。在这里,我们建立了一种基于壳聚糖的纳米复合物CE7Q / CQ / S,可在一个平台上提供分子靶向药物厄洛替尼(Er),表达Survivin shRNA表达质粒(SV)和光热剂七甲胺花菁染料(Cy7),带有表皮生长因子受体(EGFR)突变的NSCLC的红外(NIR)荧光成像和三联疗法。所获得的CE7Q / CQ / S表现出良好的光热效应,良好的DNA结合能力和pH / NIR双响应释放行为。缀合的Er可以介导Cy7向EGFR突变的NSCLC细胞的特异性传递,从而实现靶向NIR荧光成像和光热疗法(PTT)。体外和体内结果表明,Survivin表达的下调和光热效应可与Er协同作用,从而在Er敏感或Er耐药的EGFR突变NSCLC细胞中诱导令人满意的抗癌作用。通过将化学/基因/光热疗法整合到一种治疗学纳米平台中,CE7Q / CQ / S可以显着抑制EGFR突变的NSCLC,表明其在治疗NSCLC中的潜在用途。意义声明:表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)的开发提高了由EGFR突变驱动的NSCLC患者的总体生存率。不幸的是,治疗后EGFR-TKIs获得性耐药的出现几乎是不可避免的。这里,我们基于壳聚糖构建了一种近红外/ pH双响应纳米复合物CE7Q / CQ / S,可以将靶向近红外荧光成像和化学/基因/光疗三疗法结合在一起。我们发现CE7Q / CQ / S在对抗EGFR突变的NSCLC方面具有令人鼓舞的结果。Survivin表达的抑制和光热疗法的应用可以与厄洛替尼和逆转厄洛替尼耐药性协同作用。这项工作的结果表明,这种基于壳聚糖的组合治疗性纳米平台可能成为NSCLC治疗的有希望的候选者。Survivin表达的抑制和光热疗法的应用可以与厄洛替尼和逆转厄洛替尼耐药产生协同作用。这项工作的结果表明,这种基于壳聚糖的组合治疗性纳米平台可能成为NSCLC治疗的有希望的候选者。Survivin表达的抑制和光热疗法的应用可以与厄洛替尼和逆转厄洛替尼耐药性协同作用。这项工作的结果表明,这种基于壳聚糖的组合治疗性纳米平台可能成为NSCLC治疗的有希望的候选者。
更新日期:2020-03-09
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