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Light-triggered dual-modality drug release of self-assembled prodrug-nanoparticles for synergistic photodynamic and hypoxia-activated therapy.
Nanoscale Horizons ( IF 9.7 ) Pub Date : 2020-03-17 , DOI: 10.1039/d0nh00034e
Dongyang Zhao 1 , Wenhui Tao , Songhao Li , Lingxiao Li , Yixin Sun , Guanting Li , Gang Wang , Yang Wang , Bin Lin , Cong Luo , Yongjun Wang , Maosheng Cheng , Zhonggui He , Jin Sun
Affiliation  

Photodynamic therapy (PDT) leads to tumor hypoxia which could be utilized for the activation of hypoxia-activated prodrugs (HAPs). However, conventional photosensitizer-loaded nanoformulations suffer from an aggregation-caused quenching (ACQ) effect, which limits the efficiency of PDT and synergistic therapy. Herein, prodrug-nanoparticles (NPs) are prepared by the self-assembly of heterodimeric prodrugs composed of pyropheophorbide a (PPa), hypoxia-activated prodrug PR104A, and a thioether or thioketal linkage. In addition, a novel dual-modality drug release pattern is proposed on the basis of the structural states of prodrug-NPs. Under light irradiation, PR104A is released via photoinduced electron transfer (PET) due to the aggregation state of prodrugs. With the disassembly of prodrug-NPs, the ACQ effect is relieved, and PPa produces singlet oxygen which further promotes the reactive oxygen species (ROS)-sensitive release of PR104A. Such prodrug-NPs turn the disadvantage of the ACQ effect to facilitate drug release, demonstrating high-efficiency synergy in combination with PDT and hypoxia-activated therapy.

中文翻译:

自组装前药纳米颗粒的光触发双峰释放药物,用于协同光动力和缺氧激活疗法。

光动力疗法(PDT)导致肿瘤缺氧,可用于激活缺氧激活的前药(HAP)。然而,常规的光敏剂负载的纳米制剂遭受聚集引起的猝灭(ACQ)效应,这限制了PDT和协同治疗的效率。在此,前药纳米颗粒(NPs)是通过自组装由焦脱镁叶绿酸a(PPa),低氧激活的前药PR104A和硫醚或硫代缩酮键组成的异二聚体前药制备的。此外,基于前药-NPs的结构状态,提出了一种新型的双峰药物释放模式。在光照射下,由于前药的聚集状态,PR104A通过光诱导电子转移(PET)释放。随着前药NP的分解,ACQ效果得到缓解,PPA产生单线态氧,进一步促进PR104A的活性氧(ROS)敏感释放。此类前药NP改变了ACQ效应的缺点,以利于药物释放,与PDT和缺氧激活疗法联合使用显示出高效协同作用。
更新日期:2020-03-17
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