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      Cancer-targeted design of bioresponsive prodrug with enhanced cellular uptake to achieve precise cancer therapy

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      cancer-targeted.pdf (1.920Mb)
      Author
      Liang, Yuanwei
      Huang, Wei
      Zeng, Delong
      Huang, Xiaoting
      Chan, Leung
      Mei, Chaoming
      Feng, Pengju
      Tan, Choon-Hong
      Chen, Tianfeng
      Date of Issue
      2018
      School
      School of Physical and Mathematical Sciences
      Version
      Published version
      Abstract
      Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of novel anticancer drugs to enhance the cancer targeting effects and biocompatibility, and decrease toxic side effects. Camptothecin (CPT) demonstrated strong anticancer activity in clinical trials but also notorious adverse effects. In this study, we presented a smart targeted delivery system (Biotin-ss-CPT) that consists of cancer-targeted moiety (biotin), a cleavable disulfide linker (S-S bond) and the active drug CPT. Biotin-ss-CPT was found to exhibit potent effects on the migration of cancer cells and induced apoptosis by induction of ROS-mediated mitochondrial dysfunction and perturbation of GSH/GPXs system, as well as activation of caspases. In vivo tumor suppression investigation including toxicity evaluation and pathology analysis, accompanied by MR images showed that Biotin-ss-CPT can be recognized specifically and selectively and taken up preferentially by cancers cells, followed by localization and accumulation effectively in tumor site, then released CPT by biological response to achieve high therapeutic effect and remarkably reduced the side effects that free CPT caused, such as liver damage, renal injury, and weight loss to realize precise cancer therapy. Taken together, our results suggest that biotinylation and bioresponsive functionalization of anticancer drugs could be a good way for the discovery of next-generation cancer therapeutics.
      Subject
      Adverse Effects
      Cancer-targeted
      Science::Chemistry::Biochemistry
      Type
      Journal Article
      Series/Journal Title
      Drug Delivery
      Rights
      © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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      http://dx.doi.org/10.1080/10717544.2018.1477862
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