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Integrated prodrug micelles with two-photon bioimaging and pH-triggered drug delivery for cancer theranostics.
Regenerative Biomaterials ( IF 6.7 ) Pub Date : 2019-11-04 , DOI: 10.1093/rb/rbz035
Hong Xu 1 , Boxuan Ma 1 , Jizhou Jiang 2 , Sutong Xiao 2 , Rongrong Peng 2 , Weihua Zhuang 1 , Gaocan Li 1 , Yunbing Wang 1
Affiliation  

Nanodrug carriers with fluorescence radiation are widely used in cancer diagnosis and therapy due to their real-time imaging, less side effect, better drug utilization as well as the good bioimaging ability. However, traditional nanocarriers still suffer from unexpectable drug leakage, unsatisfactory tumor-targeted drug delivery and shallow imaging depth, which limit their further application in cancer theranostics. In this study, an integrated nanoplatform is constructed by polymeric prodrug micelles with two-photon and aggregation-induced emission bioimaging, charge reversal and drug delivery triggered by acidic pH. The prodrug micelles can be self-assembled by the TP-PEI (DA/DOX)-PEG prodrug polymer, which consists of the two-photon fluorophore (TP), dimethylmaleic anhydride (DA) grafted polyethyleneimine (PEI) and polyethylene glycol (PEG). The PEG segment, DOX and DA are bridged to polymer by acid cleavable bonds, which provides the micelles a 'stealth' property and a satisfactory stability during blood circulation, while the outside PEG segment is abandoned along with the DA protection in the tumor acidic microenvironment, thus leading to charge reversal-mediated accelerated endocytosis and tumor-targeted drug delivery. The great antitumor efficacy and reduced side effect of these pH-sensitive prodrug micelles are confirmed by antitumor assays in vitro and in vivo. Meanwhile, these micelles exhibited great deep-tissue two-photon bioimaging ability up to 150 μm in depth. The great antitumor efficacy, reduced side effect and deep two-photon tissue imaging make the TP-PEI (DA/DOX)-PEG prodrug micelles would be an efficient strategy for theranostic nanoplatform in cancer treatment.

中文翻译:

具有双光子生物成像和pH触发药物递送功能的整合前药胶束,用于癌症治疗学。

具有荧光辐射的纳米药物载体由于其实时成像,副作用少,药物利用性好以及良好的生物成像能力而被广泛用于癌症的诊断和治疗。然而,传统的纳米载体仍然遭受不可预期的药物泄漏,不能令人满意地靶向肿瘤的药物递送和浅的成像深度,这限制了它们在癌症治疗学中的进一步应用。在这项研究中,通过聚合前药胶束构建了一个集成的纳米平台,该胶束具有双光子和聚集诱导的发射生物成像,电荷逆转以及由酸性pH触发的药物递送。前药胶束可以通过TP-PEI(DA / DOX)-PEG前药聚合物自组装,该聚合物由双光子荧光团(TP),二甲基马来酸酐(DA)接枝的聚乙烯亚胺(PEI)和聚乙二醇(PEG)组成。 )。PEG片段,DOX和DA通过酸可裂解键桥接到聚合物上,这为胶束提供了“隐身”特性和在血液循环中令人满意的稳定性,而外部PEG片段与DA在肿瘤酸性微环境中的保护一起被废弃了,从而导致电荷逆转介导的加速内吞作用和靶向肿瘤的药物递送。这些pH敏感的前药胶束的出色的抗肿瘤功效和降低的副作用已通过体外和体内抗肿瘤试验得以证实。同时,这些胶束在深度高达150μm时表现出很大的深层双光子生物成像能力。强大的抗肿瘤功效
更新日期:2019-11-04
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