Reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) micelles: synthesis and CD44-mediated potent delivery of docetaxel to triple negative breast tumor in vivo
| Autor: | Liang Cheng, Jian Zhang, Jan Feijen, Yaqin Zhu, Zhiyuan Zhong, Fenghua Meng |
|---|---|
| Přispěvatelé: | Biomaterials Science and Technology |
| Rok vydání: | 2018 |
| Předmět: |
Biomedical Engineering
02 engineering and technology 010402 general chemistry 01 natural sciences Micelle Flow cytometry chemistry.chemical_compound In vivo Hyaluronic acid medicine General Materials Science biology medicine.diagnostic_test Chemistry CD44 General Chemistry General Medicine 021001 nanoscience & nanotechnology n/a OA procedure In vitro 0104 chemical sciences Docetaxel biology.protein Biophysics Trimethylene carbonate 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Materials Chemistry B, 6(19), 3040-3047. Royal Society of Chemistry |
| ISSN: | 2050-7518 2050-750X |
| DOI: | 10.1039/c8tb00094h |
| Popis: | Future cancer therapy relies on the development of simple, selective and bioresponsive nanomedicines. Herein, we report that reduction-responsive core-crosslinked hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) micelles (HA-CCMs) can be easily synthesized and achieve efficient CD44-mediated delivery and triggered cytoplasmic release of docetaxel (DTX) to MDA-MB-231 human triple negative breast tumor in vivo. DTX-loaded HA-CCMs exhibited a favorable size of 85 nm, low drug leakage and glutathione-responsive DTX release. HA-CCMs were efficiently taken up by CD44-overexpressing MDA-MB-231 cells as indicated by flow cytometry. DTX-loaded HA-CCMs induced selective apoptotic activity toward MDA-MB-231 cells in vitro. Notably, over 7-fold longer blood circulation time and 4-fold stronger tumor accumulation were observed for DTX-loaded HA-CCMs compared to free DTX. Cy5-labeled HA-CCMs revealed deep tumor penetration at 6 h post injection. DTX-loaded HA-CCMs were shown to effectively suppress the progression of MDA-MB-231 tumor and significantly extend mice survival time. These hyaluronic acid-shelled and disulfide-crosslinked micelles with great simplicity and selectivity are highly promising for treating various CD44-overexpressing cancers. |
| Databáze: | OpenAIRE |
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