Chemoenzymatic synthesis of dual-responsive graft copolymers for drug delivery: long-term stability, high loading and cell selectivity
| Autor: | Bei-Yu Liu, Xiao-Qi Yu, Yan-Hong Liu, Jun Li, Na Wang, Xian-Ling Yang, Wan-Xia Wu |
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| Rok vydání: | 2020 |
| Předmět: |
Biomedical Engineering
02 engineering and technology General Chemistry General Medicine 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Micelle 0104 chemical sciences chemistry.chemical_compound chemistry Critical micelle concentration Amphiphile Drug delivery Cancer cell Biophysics Doxorubicin Hydrochloride General Materials Science Nanocarriers 0210 nano-technology Ethylene glycol |
| Zdroj: | Journal of materials chemistry. B. 6(43) |
| ISSN: | 2050-7518 |
| Popis: | A series of amphiphilic graft copolymers, poly(N-propargyldiethanolamine 4,4'-dithiodibutyionate)-graft-monomethoxy poly(ethylene glycol) (PPD-g-mPEG), were designed via a chemoenzymatic method for pH and reduced glutathione (GSH) dual-responsive drug delivery. The effects of percent grafting and molecular weights of mPEG on critical micelle concentration (CMC) values, size of micelles, drug loading and dual-response were tested. The graft copolymers could easily form homogeneous spherical micelles with appropriate sizes and zeta-potentials. The micelles of PPD-g-mPEG copolymers loaded doxorubicin (DOX) in high efficiency, and showed excellent stability under physiological conditions and synergetic dual-response to weakly acidic pH and GSH. In vitro experiments confirmed that the DOX-loaded micelles could be internalized into cancer cells efficiently and release DOX over time. Furthermore, cell cytotoxicity assays indicated that the graft copolymers were non-cytotoxic to both cancerous and normal cells while the DOX-loaded micelles greatly improved the selectivity ratios between HeLa cells and HL-7702 cells. DOX-loaded micelles also avoided hemolysis of red blood cells (RBCs) effectively compared with commercialized doxorubicin hydrochloride. All these demonstrated the potential of PPD-g-mPEG as a model to create more functional dual-responsive nanocarriers for controlled drug delivery. |
| Databáze: | OpenAIRE |
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