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PH-sensitive Polymeric Micelles Triggered Drug Release For Extracellular And Intracellular Drug Targeting Delivery

Liu Yan-hua, W. Wang, J. Yang, C. Zhou, Jin Sun
Published 2013 · Chemistry

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Abstract Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy. Based on physiological differences between the normal tissue and the tumor tissue, one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems. The copolymers with reversible protonation–deprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release. These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect, or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway. The pH-sensitive micelles have been proved the specific tumor cell targeting, enhanced cellular internalization, rapid drug release, and multidrug resistance reversal. The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting. The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells, which reverses multidrug resistance. The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy, and is a novel promising platform for tumor-targeting drug delivery.
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