Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin
| Autor: | Chun Liu, Xue-nong Zhang, Zhi-qiang Yuan, Yan Tang, Wei-liang Chen, Fang Li, Shu-di Yang, Yang Liu, Ji-zhao Li, Xiao-feng Zhou |
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| Rok vydání: | 2017 |
| Předmět: |
efficient delivery
Intracellular pH Biophysics Drug Evaluation Preclinical Pharmaceutical Science Bioengineering 02 engineering and technology Enhanced permeability and retention effect stepwise pH-responsive 010402 general chemistry 01 natural sciences Biomaterials Drug Delivery Systems International Journal of Nanomedicine Cell Line Tumor Drug Discovery medicine Extracellular Animals Doxorubicin Tissue Distribution Particle Size Cytotoxicity Original Research Chitosan Drug Carriers Mice Inbred BALB C Antibiotics Antineoplastic Chemistry Organic Chemistry Urocanic Acid technology industry and agriculture General Medicine Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology on-demand drug release Malonates 0104 chemical sciences Drug Liberation Nanoparticles Female Nanocarriers 0210 nano-technology Drug carrier charge reversal Intracellular medicine.drug |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Wei-liang Chen,1 Fang Li,1 Yan Tang,1 Shu-di Yang,1 Ji-zhao Li,1 Zhi-qiang Yuan,1 Yang Liu,1 Xiao-feng Zhou,2 Chun Liu,3 Xue-nong Zhang1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 2Department of Ultrasound, Changshu Hospital of Traditional Chinese Medicine, Changshu, 3Department of Pharmacy, The Hospital of Suzhou People’s Hospital Affiliated to Nanjing Medical University, Suzhou, People’s Republic of China Abstract: Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents. Keywords: stepwise pH-responsive, charge reversal, on-demand drug release, efficient delivery |
| Databáze: | OpenAIRE |
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