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- Title
A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging.
- Authors
An, Hong-Wei; Li, Li-Li; Wang, Yi; Wang, Ziqi; Hou, Dayong; Lin, Yao-Xin; Qiao, Sheng-Lin; Wang, Man-Di; Yang, Chao; Cong, Yong; Ma, Yang; Zhao, Xiao-Xiao; Cai, Qian; Chen, Wen-Ting; Lu, Chu-Qi; Xu, Wanhai; Wang, Hao; Zhao, Yuliang
- Abstract
Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders. The activation of drugs within cellular systems may provide targeted therapies for cancer. Here, the authors make a drug delivery system that is activated within the cell and exploits XIAP expression to cleave a linker region, resulting in the self-assembly of the system and drug release within cancer cells.
- Subjects
TUMORS; CANCER cells; RETICULO-endothelial system; DRUG activation; NANOSTRUCTURED materials
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-12848-5