Virus-Inspired Gold Nanorod-Mesoporous Silica Core−Shell Nanoparticles Integrated with tTF-EG3287 for Synergetic Tumor Photothermal Therapy and Selective Therapy for Vascular Thrombosis
Virus-Inspired Gold Nanorod-Mesoporous Silica Core−Shell Nanoparticles Integrated with tTF-EG3287 for Synergetic Tumor Photothermal Therapy and Selective Therapy for Vascular Thrombosis
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病毒启发的金纳米棒-介孔二氧化硅核壳纳米颗粒与 tTF-EG3287 集成，用于协同肿瘤光热治疗和血管血栓形成的选择性治疗
DOI：
10.1021/acsami.1c11947
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发表时间：
2021
影响因子：
9.5
通讯作者：
Jianghua Yan
中科院分区：
文献类型：
--
作者：
Xian Luo;Jun Xie;Zonglang Zhou;Shan Ma;Li Wang;Mengqi Li;Jiajing Liu;Peiyuan Wang;Yang Li;Fanghong Luo;Jianghua Yan
协同治疗包括两种或多种常规治疗方法的组合，可以通过结合每种治疗方法的优点并避免缺点来用于肿瘤治疗。在本研究中，合成了截短组织因子（tTF）-EG3287融合蛋白封装的金纳米棒（GNR）-病毒启发的介孔二氧化硅核壳纳米颗粒（乙烯基杂化二氧化硅纳米颗粒；VSNP）（GNR@VSNP-tTF-EG3287），以实现协同治疗 利用选择性血管血栓治疗（SVTT）和光热疗法（PTT）。通过整合tTF-EG3287的靶向凝血活性和GNR@VSNP的高肿瘤消融作用，局部热疗可以利用近红外光诱导高比例的血管内皮细胞凋亡。这为 tTF-EG3287 提供了额外的磷脂位点，并增强了其体外促凝血活性。此外，纳米颗粒具有独特的拓扑病毒结构，表现出优异的细胞摄取特性，从而具有显着的抗肿瘤功效。体内抗肿瘤结果进一步证明了SVTT和PTT之间的相互作用，而协同治疗（SVTT和PTT）取得了增强的效果，优于每种方式各自的治疗效果或各自疗效的叠加效果。总之，合成的GNR@VSNP-tTF-EG3287通过避免多次注射和次优给药发挥协同作用并提高抗肿瘤效率。这些效应同时影响肿瘤血液供应和癌细胞增殖。数据表明，tTF-EG3287 诱导的 SVTT 和 PTT 的整合可以为协同肿瘤治疗提供潜在的策略。
Synergetic therapy includes the combination of two or more conventional therapeutic approaches and can be used for tumor treatment by combining the advantages and avoiding the drawbacks of each type of treatment. In the present study, truncated tissue factor (tTF)-EG3287 fusion protein-encapsulated gold nanorod (GNR)-virus-inspired mesoporous silica core–shell nanoparticles (vinyl hybrid silica nanoparticles; VSNP) (GNR@VSNP-tTF-EG3287) were synthesized to achieve synergetic therapy by utilizing selective vascular thrombosis therapy (SVTT) and photothermal therapy (PTT). By integrating the targeted coagulation activity of tTF-EG3287 and the high tumor ablation effect of GNR@VSNP, local hyperthermia could induce a high percentage of apoptosis of vascular endothelial cells by using near-infrared light. This provided additional phospholipid sites for tTF-EG3287 and enhanced its procoagulant activityin vitro. In addition, the nanoparticles, which had unique topological viral structures, exhibited superior cellular uptake properties leading to significant antitumor efficacy. Thein vivoantitumor results further demonstrated an interaction between SVTT and PTT, whereas the synergetic therapy (SVTT and PTT) achieved an enhanced effect, which was superior to the respective treatment efficacy of each modality or the additive effect of their individual efficacies. In summary, the synthesized GNR@VSNP-tTF-EG3287 exerted synergetic effects and enhanced the antitumor efficiency by avoiding multiple injections and suboptimal administration. These effects simultaneously affected both tumor blood supply and cancer cell proliferation. The data suggested that the integration of SVTT induced by tTF-EG3287 and PTT could provide potential strategies for synergetic tumor therapy.