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Multi-Activated Polymeric Micelles with Charge-Conversion and ROS-Controlled Drug Release for Efficient Cancer Therapy

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Insufficient cellular uptake and undesirable drug release in specific sites remain a serious obstacle to achieve successful antitumor therapy. Herein, a new polymeric micelle with ROS sensitive thioketal (TK) moiety and pH responsive imidazole (IMD) was developed for tumor-specific targeting and ROS-activated drug release. The multi-activated micelles with the mean diameter around 150 nm could efficiently encapsulate anticancer drug doxorubicin (DOX). The size and zeta potential as well as drug release profiles of the micelles confirmed that lower pH and higher ROS concentration in tumors induced the protonation of imidazole and the cleavage of thioketal to result in pH dependent extracellular cellular uptake, endosomal escape and ROS-activated intracellular drug release. Flow cytometry (FACS) and confocal laser scanning microscopy (CLSM) results demonstrated that the dual pH and ROS-activated DOX-loaded micelles could markedly enhance the internalization efficiency and trigger fast drug release in cytoplasm. The in vivo study revealed that the pH and ROS-activated micelles not only exhibited promising anticancer activity but also eliminate the systemic toxicity of DOX. This work sets up a facile strategy to construct innovative multi-function polymeric micelles to overcome the hurdles in anticancer drug delivery.
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Keywords: PH-DEPENDENT; POLYMERIC MICELLES; ROS-ACTIVATED; THIOKETAL; π–π STACKING

Document Type: Research Article

Publication date: August 1, 2017

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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