Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity for intelligent co-delivery of paclitaxel and siRNA to breast tumor
| Autor: | Yang Liu, Ben-gang You, Wen-jing Zhu, Qiao-Ling Zhu, Chen-xi Qu, Zhi-qiang Yuan, Shu-di Yang, Fang Li, Xue-nong Zhang, Wei-liang Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Small interfering RNA
Abcg2 Polymers Pharmaceutical Science 02 engineering and technology co-delivery chemistry.chemical_compound 0302 clinical medicine RNA interference International Journal of Nanomedicine Drug Discovery Tissue Distribution RNA Small Interfering Micelles Original Research Drug Carriers biology Chemistry General Medicine environmentally sensitive Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Drug Resistance Multiple Lipoproteins LDL Paclitaxel 030220 oncology & carcinogenesis MCF-7 Cells Female RNA Interference 0210 nano-technology Oxidation-Reduction Biophysics Mice Nude Bioengineering Breast Neoplasms Enhanced permeability and retention effect Biomaterials 03 medical and health sciences multidrug resistance Cell Line Tumor micelle Gene silencing Animals Humans tumor targeting Organic Chemistry Multiple drug resistance Drug Liberation LDL receptor Cancer research biology.protein |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Wen-jing Zhu,1,* Shu-di Yang,1,* Chen-xi Qu,1 Qiao-ling Zhu,1,2 Wei-liang Chen,1 Fang Li,1 Zhi-qiang Yuan,1 Yang Liu,1 Ben-gang You,1 Xue-nong Zhang1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 2Department of Clinical Medicine, Nanjing Gulou Hospital, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR) is a major obstacle for the clinical therapy of malignant human cancers. The discovery of RNA interference provides efficient gene silencing within tumor cells for reversing MDR. In this study, a new “binary polymer” low-density lipoprotein–N-succinyl chitosan–cystamine–urocanic acid (LDL–NSC–SS–UA) with dual pH/redox sensitivity and targeting effect was synthesized for the co-delivery of breast cancer resistance protein small interfering RNA (siRNA) and paclitaxel (PTX). In vivo, the co-delivering micelles can accumulate in tumor tissue via the enhanced permeability and retention effect and the specific recognition and combination of LDL and LDL receptor, which is overexpressed on the surface of tumor cell membranes. The siRNA–PTX-loaded micelles inhibited gene and drug release under physiological conditions while promoting fast release in an acid microenvironment or in the presence of glutathione. The micelles escaped from the lysosome through the proton sponge effect. Additionally, the micelles exhibited superior antitumor activity and downregulated the protein and mRNA expression levels of breast cancer resistance protein in MCF-7/Taxol cells. The biodistribution and antitumor studies proved that the siRNA–PTX-loaded micelles possessed prolonged circulation time with a remarkable tumor-targeting effect and effectively inhibited tumor growth. Therefore, the novel dual pH/redox-sensitive polymers co-delivering siRNA and PTX with excellent biocompatibility and effective reversal of MDR demonstrate a considerable potential in cancer therapy. Keywords: multidrug resistance, micelle, co-delivery, environmentally sensitive, tumor targeting |
| Databáze: | OpenAIRE |
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