A pH‐Responsive Carrier System that Generates NO Bubbles to Trigger Drug Release and Reverse P‐Glycoprotein‐Mediated Multidrug Resistance |
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| Authors: | Ming‐Fan Chung Hung‐Yi Liu Dr Kun‐Ju Lin Dr Wei‐Tso Chia Prof Hsing‐Wen Sung |
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| Institution: | 1. Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan (ROC);2. Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan (ROC);3. Department of Orthopaedics, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan (ROC) |
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| Abstract: | Multidrug resistance (MDR) resulting from the overexpression of drug transporters such as P‐glycoprotein (Pgp) increases the efflux of drugs and thereby limits the effectiveness of chemotherapy. To address this issue, this work develops an injectable hollow microsphere (HM) system that carries the anticancer agent irinotecan (CPT‐11) and a NO‐releasing donor (NONOate). Upon injection of this system into acidic tumor tissue, environmental protons infiltrate the shell of the HMs and react with their encapsulated NONOate to form NO bubbles that trigger localized drug release and serve as a Pgp‐mediated MDR reversal agent. The site‐specific drug release and the NO‐reduced Pgp‐mediated transport can cause the intracellular accumulation of the drug at a concentration that exceeds the cell‐killing threshold, eventually inducing its antitumor activity. These results reveal that this pH‐responsive HM carrier system provides a potentially effective method for treating cancers that develop MDR. |
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| Keywords: | antitumor agents cancer drug delivery fluorescence microscopy multidrug resistance |
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