Zheng Ziliang, Chen Qi, Dai Rong, Jia Zhuo, Yang Chenhua, Peng Xiaoyang, Zhang Ruiping
Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China and The Affiliated Da Yi Hospital of Shanxi Medical University, Taiyuan 030032, China.
College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024, China.
Nanoscale. 2020 Jun 4;12(21):11562-11572. doi: 10.1039/d0nr02543g.
Nanosystems responsive to a tumor microenvironment (TME) have recently attracted great attention due to their potential in precision cancer theranostics. However, theranostic nanosystems with a TME-activated consecutive cascade for the accurate diagnosis and treatment of cancer have rarely been exploited. Herein, an activatable theranostic nanosystem (Bi2S3-Ag2S-DATS@BSA-N3 NYs) is designed and constructed on the basis of a one-pot biomineralization method and surface functional modification to improve second near-infrared (NIR-II) fluorescence/photoacoustic (PA) imaging-guided photothermal therapy (PTT)/gas therapy (GT). Based on enhanced penetration and retention (EPR) effect-mediated tumor accumulation, the tumor-overexpressed glutathione (GSH) can accelerate hydrogen sulfide (H2S) generation from the nanoparticles by reacting with the encapsulated diallyl trisulfide (DATS). Meanwhile, the in situ released H2S can be used not only for gas therapy, but also to start the reduction of -N3(-) to -NH2(+), thereby enhancing the tumor-specific aggregation of NYs. As a result, the activatable nanosystems with excellent tumor accumulation and biodistribution could achieve an accurate NIR-II/PA dual-modality imaging for guiding the synergistic anticancer efficacy (PTT/GT). Thus, this work provides a promising TME-mediated continuously responsive strategy for efficient anticancer therapy.
由于纳米系统在精准癌症诊疗方面的潜力，对肿瘤微环境（TME）有响应的纳米系统最近备受关注。然而，具有TME激活的连续级联反应以实现癌症准确诊断和治疗的诊疗纳米系统却鲜有研究。在此，基于一锅法生物矿化和表面功能修饰，设计并构建了一种可激活的诊疗纳米系统（Bi2S3-Ag2S-DATS@BSA-N3 NYs），以改善近红外二区（NIR-II）荧光/光声（PA）成像引导下的光热疗法（PTT）/气体疗法（GT）。基于增强的渗透与滞留（EPR）效应介导的肿瘤蓄积，肿瘤中高表达的谷胱甘肽（GSH）可通过与包裹的二烯丙基三硫醚（DATS）反应，加速纳米颗粒产生硫化氢（H2S）。同时，原位释放的H2S不仅可用于气体疗法，还能引发-N3(-)向-NH2(+)的还原，从而增强纳米囊泡（NYs）的肿瘤特异性聚集。结果，具有优异肿瘤蓄积和生物分布的可激活纳米系统能够实现准确的NIR-II/PA双模态成像，以指导协同抗癌疗效（PTT/GT）。因此，这项工作为高效抗癌治疗提供了一种有前景的TME介导的持续响应策略。
