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首页> 外文期刊>Advanced Functional Materials >Size Switchable Nanoclusters Fueled by Extracellular ATP for Promoting Deep Penetration and MRI-Guided Tumor Photothermal Therapy
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Size Switchable Nanoclusters Fueled by Extracellular ATP for Promoting Deep Penetration and MRI-Guided Tumor Photothermal Therapy

机译：细胞外ATP促进大小可转换的纳米团簇，以促进深层穿透和MRI指导的肿瘤光热疗法

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Protein-based theranostic agents (PBTAs) exhibit superior performance in the diagnosis and therapy of cancers. However, the in vivo applications of PBTA are largely limited by undesired accumulation, penetration, or selectivity. Here, an ATP-supersensitive protein cluster is fabricated for promoting PBTA delivery and enhancing magnetic resonance imaging (MRI)-guided tumor photothermal therapy. Gd3+- and CuS-coloaded small bovine serum albumin nanoparticles (GdCuB) are synthesized as the model protein with a size of 9 nm and are encapsulated into charge switchable polycations (DEP) to form DEP/GdCuB nanoclusters of 120 nm. In blood circulation, DEP/GdCuB significantly extends the half-lifetime and thereby enhances the tumor accumulation of GdCuB. When the clusters reach the tumor site, the extracellular adenosine triphosphate (ATP) can effectively trigger the release of GdCuB, resulting in tumoral deep penetration as well as the activation of T-1-weighted MRI (r(1) value switched from 2.8 x 10(-3) to 11.8 x 10(-3) m(-1) s(-1)). Furthermore, this delivery strategy also improves the tumoral photothermal therapy efficacy with the MRI-guided therapy. The study of ATP-activated nanoclusters develops a novel strategy for tumor deep penetration and on/off imaging of PBTA by size switchable technology, and reveals the potential for MRI-guided therapy of cancers.
机译：基于蛋白质的治疗药物（PBTA）在癌症的诊断和治疗中表现出卓越的性能。但是，PBTA的体内应用在很大程度上受到不希望的积累，渗透或选择性的限制。在这里，制造了ATP超敏蛋白簇，以促进PBTA递送并增强磁共振成像（MRI）指导的肿瘤光热疗法。合成了Gd3 +和CuS负载的小牛血清白蛋白纳米颗粒（GdCuB）作为模型蛋白，大小为9 nm，并封装到电荷可切换聚阳离子（DEP）中，形成120 nm的DEP / GdCuB纳米簇。在血液循环中，DEP / GdCuB显着延长了半衰期，从而增强了GdCuB的肿瘤蓄积。当簇到达肿瘤部位时，细胞外三磷酸腺苷（ATP）可以有效触发GdCuB的释放，导致肿瘤深层穿透以及T-1加权MRI的激活（r（1）值从2.8 x 10（-3）到11.8 x 10（-3）m（-1）s（-1））。此外，该递送策略还通过MRI引导的疗法改善了肿瘤光热疗法的功效。 ATP激活的纳米簇的研究为肿瘤的深层渗透和通过大小转换技术对PBTA的开/关成像开发了一种新的策略，并揭示了MRI指导的癌症治疗潜力。

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