Nucleolin-Targeting AS1411-Aptamer-Modified Graft Polymeric Micelle with Dual pH/Redox Sensitivity Designed To Enhance Tumor Therapy through the Codelivery of Doxorubicin/TLR4 siRNA and Suppression of Invasion
| Autor: | Ying Wang, Yang Liu, Ben-gang You, Chen-xi Qu, Wei-liang Chen, Meng-tian Chen, Xue-nong Zhang, Zhaoxiang Ren, Shu-di Yang |
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| Rok vydání: | 2017 |
| Předmět: |
Cell Survival
Polymers Aptamer Pharmaceutical Science 02 engineering and technology 010402 general chemistry 01 natural sciences Micelle Mice In vivo Drug Discovery medicine Animals Humans Doxorubicin RNA Small Interfering Cytotoxicity Micelles A549 cell Drug Carriers Chemistry RNA-Binding Proteins Phosphoproteins 021001 nanoscience & nanotechnology 0104 chemical sciences Drug Liberation A549 Cells Biophysics Molecular Medicine 0210 nano-technology Drug carrier Nucleolin medicine.drug |
| Zdroj: | Molecular Pharmaceutics. 15:314-325 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.7b01093 |
| Popis: | In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4-siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox-siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Furthermore, the micelles loaded with TLR4-siRNA inhibited the migration and invasion of A549. Excellent tumor penetrating efficacy was also noted in the A549 tumor spheroids and solid tumor slices. In vivo, multiple results demonstrated the excellent tumor-targeting ability of AS1411-chitosan-ss-polyethylenimine-urocanic acid (ACPU) micelle in tumor tissues. The micelles exhibited excellent antitumor efficacy and low toxicity in the systemic circulation in lung-tumor-bearing BALB/c mice. These results conclusively demonstrated the great potential of the new graft copolymer micelle with targeting function for the targeted and efficient codelivery of chemotherapeutic drugs and genes in cancer treatment. |
| Databáze: | OpenAIRE |
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