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A targeting theranostics nanomedicine as an alternative approach for hyperthermia perfusion
Biomaterials ( IF 14.0 ) Pub Date : 2018-04-12 , DOI: 10.1016/j.biomaterials.2018.04.016
Tao Sun , Guangping Zhang , Qingbing Wang , Qinjun Chen , Xinli Chen , Yifei Lu , Lisha Liu , Yu Zhang , Xi He , Chunhui Ruan , Yujie Zhang , Qin Guo , Chen Jiang

Real-time monitoring drug-release is often regarded crucial in theranostics nanomedicine design, since it provides precise establishment of spatio-temporal activation of the drug-release in vitro and in vivo. A symmetrical self-immolative drug-dye conjugation (DDC) prodrug is developed in this study with disulfide bond as the trigger. The prodrug can be escorted by targeting PEG-PLGA micelles and hereby accumulated in the tumor by both active and passive targeting effect. Glutathione (GSH) with higher concentration in the tumor microenvironment can readily cleave the disulfide bond to initiate a subsequent decomposition of DDC, where the drug and dye can be released simultaneously in a strict one-to-one mode. Upon the disintegration, the “Turned-On” probe can emit near-infrared (NIR) fluorescence, with the aim of providing accurate and real-time information for the prodrugs' activation and biodistribution in vivo in a non-invasive way. Furthermore, the released dye can meanwhile act as a photothermic sensitizer, which can in-situ assist a deep penetration for the released drug in the tumor tissue with enhanced therapeutic efficiency. This “babysitting” strategy provides new reference for designing versatile theranostic nanomedicines for preclinical evaluations and an alternative approach for hyperthermia perfusion in clinic.



中文翻译:

靶向治疗学纳米医学作为热疗灌注的替代方法

实时监测药物释放通常被认为是治疗学纳米药物设计中的关键,因为它提供了体外体内药物释放时空激活的精确建立。。在这项研究中,以二硫键为触发剂,开发了一种对称的自消灭性药物-染料共轭(DDC)前药。可以通过靶向PEG-PLGA胶束来护送前药,并由此通过主动和被动靶向作用在肿瘤中积累。肿瘤微环境中浓度较高的谷胱甘肽(GSH)可以轻易裂解二硫键以引发DDC的后续分解,在该过程中,药物和染料可以严格的一对一方式同时释放。解体后,“ Turned-On”探针可以发射近红外(NIR)荧光,目的是为前药在体内的活化和生物分布提供准确和实时的信息。以非侵入性的方式。此外,释放的染料可以同时充当光热敏化剂,其可以原位辅助释放的药物在肿瘤组织中的深层渗透,并具有增强的治疗效率。这种“保姆”策略为设计用于临床前评估的多功能治疗药物纳米药物提供了新的参考,并为临床热疗灌注的替代方法提供了参考。

更新日期:2018-07-14
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