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Cancer-specific chemotherapeutic strategy based on the vitamin K3 mediated ROS regenerative feedback and visualized drug release in vivo

Author:
Yang, Gang-Gang, Zhang, Hang, Zhang, Dong-Yang, Cao, Qian, Yang, Jing, Ji, Liang-Nian, Mao, Zong-Wan
Source:
Biomaterials 2018 v.185 pp. 73-85
ISSN:
0142-9612
Subject:
adverse effects, antineoplastic agents, drug therapy, encapsulation, fluorescence, menadione, nanoparticles, neoplasm cells, ruthenium
Abstract:
A promising theranostic nanosystem VK3-CPT@Ru-CD is designed and fabricated by the host-guest driven self-assembly between the fluorescent adamantine-functionalized Ru(II) complexes and the ROS-labile-cyclodextrin modified thioketal linkers, in which anticancer drug camptothecin (CPT) and vitamin K3 (VK3) are effectively co-encapsulated. On account of the generative feedback between the intracellular redox cycling of VK3 and the high degree of ROS-triggered collapse of nanoparticles, VK3-CPT@Ru-CD can facilitate cancer-specific ROS amplification and drug release selectively in cancer cells, thus realizing the selective killing of tumor with minimal side-effects both in vitro and in vivo, the therapeutic effect of which is more prominent than the free anti-cancer drugs. More interestingly, the menadione structure of encapsulated VK3 can effectively quench the inherent fluorescence of Ru-CD, and a fluorescence lightening up phenomenon is observed accompanied with the ROS-triggered drug release, which can be utilized for real-time tracking of drug release in vitro and in vivo.
Agid:
6131521