Cascade-Targeting of Charge-Reversal and Disulfide Bonds Shielding for Efficient DOX Delivery of Multistage Sensitive MSNs-COS-SS-CMC
| Autor: | Hao Liu, Suqin He, Shuangxia Wu, Lan Cui, Chengshen Zhu, Zhenya Zhang, Wentao Liu, Xinchang Pang, Qian Qin |
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| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
Endosome media_common.quotation_subject Biophysics Pharmaceutical Science Bioengineering macromolecular substances 02 engineering and technology 010402 general chemistry Endocytosis 01 natural sciences Biomaterials HeLa chemistry.chemical_compound Drug Discovery polycyclic compounds Internalization media_common biology Chemistry Organic Chemistry technology industry and agriculture General Medicine Glutathione 021001 nanoscience & nanotechnology biology.organism_classification In vitro 0104 chemical sciences carbohydrates (lipids) Vesicular transport protein Cancer cell 0210 nano-technology |
| Zdroj: | International Journal of Nanomedicine. 15:6153-6165 |
| ISSN: | 1178-2013 |
| Popis: | Background Although pH and redox sensitiveness have been extensively investigated to improve therapeutic efficiency, the effect of disulfide bonds location and pH-triggered charge-reversal on cascade-targeting still need to be further evaluated in cancer treatment with multi-responsive nanoparticles. Purpose The aim of this study was to design multi-responsive DOX@MSNs-COS-NN-CMC, DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS and systematically investigate the effects of disulfide bonds location and charge-reversal on the cancer cell specificity, endocytosis mechanisms and antitumor efficiency. Results In vitro drug release rate of DOX@MSNs-COS-SS-CMC in tumor environments was 7-fold higher than that under normal physiological conditions after 200 h. Furthermore, the fluorescence intensity of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS was 1.9-fold and 1.3-fold higher than free DOX at pH 6.5 and 10 mM GSH. In addition, vesicular transport might be a factor that affects the uptake efficiency of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS. The clathrin-mediated endocytosis and endosomal escape of DOX@MSNs-COS-SS-CMC enhanced cellular internalization and preserved highly controllable drug release into the perinuclear of HeLa cells. DOX@MSNs-COS-SS-CMC exhibited a synergistic chemotherapy in preeminent tumor inhibition and less side effects of cardiotoxicity. Conclusion The cascade-targeting of charge-reversal and disulfide bonds shielding would be a highly personalized strategy for cervical cancer treatment. |
| Databáze: | OpenAIRE |
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