Metal-coordinated nanomedicine for combined tumor therapy by inducing paraptosis and apoptosis
| Autor: | Yi-Bin Liu, Xiayun Chen, Xian‐Tong Chen, Rong-Rong Zheng, Xi-Yong Yu, Hong Cheng, Chang Wang, Ling-Shan Liu, Shi-Ying Li, Lin-Ping Zhao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Programmed cell death Chemistry Endoplasmic reticulum Pharmaceutical Science Apoptosis Combination chemotherapy 02 engineering and technology Mitochondrion Endoplasmic Reticulum 021001 nanoscience & nanotechnology Paraptosis 03 medical and health sciences Nanomedicine Vacuolization Doxorubicin Cell Line Tumor medicine Cancer research 0210 nano-technology 030304 developmental biology medicine.drug |
| Zdroj: | Journal of Controlled Release. 336:159-168 |
| ISSN: | 0168-3659 |
| Popis: | Apoptosis resistance of tumor cells often results in chemoresistance and treatment failure in clinic. In this work, a Cu2+-coordinated morusin/doxorubicin biological organizer (designated as COMBO) is designed to combat cellular resistance to apoptosis for combined tumor therapy. By virtue of the coordination and π-π stacking effects, the self-assembled COMBO possesses nanometer particle size, narrow and homogenous graininess distribution as well as a good dispersion stability. Moreover, COMBO could be disassembled by glutathione (GSH) with an effective drug release and fluorescence recovery. Morusin-mediated paraptosis could induce extensive vacuolization through the dilation of endoplasmic reticulum (ER) and mitochondria, leading to non-apoptotic programmed cell death (PCD) regardless of the cellular resistance to apoptosis. Furthermore, the released doxorubicin prefers to locate in cell nucleus to cause cell apoptosis for combined chemotherapy. By the joint action of paraptosis and apoptosis, COMBO exhibits a great superiority over monotherapy in tumor inhibition with a low system toxicity. This study may open a window in the development of self-delivery nanomedicine for overcoming apoptosis resistance in tumor therapy. |
| Databáze: | OpenAIRE |
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