1. Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer.
- Author
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Zhuang J, Chen S, Hu Y, Yang F, Huo Q, and Xie N
- Subjects
- Animals, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Breast Neoplasms pathology, Cell Death drug effects, Cell Line, Tumor, Cell Movement drug effects, Cell Survival drug effects, Delayed-Action Preparations pharmacology, Delayed-Action Preparations therapeutic use, Doxorubicin pharmacology, Drug Carriers chemistry, Endocytosis drug effects, Female, HEK293 Cells, Humans, Mice, Inbred BALB C, Mice, Nude, Nanoparticles ultrastructure, Neoplasm Invasiveness, Neoplasm Metastasis, Oxidation-Reduction, Porosity, RNA, Small Interfering pharmacology, Tissue Distribution drug effects, Mice, Breast Neoplasms drug therapy, Doxorubicin therapeutic use, Nanoparticles chemistry, RNA, Small Interfering administration & dosage, Silicon Dioxide chemistry
- Abstract
Introduction: Metastatic breast cancer seriously harms women's health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects., Methods: The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds., Results: The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis., Conclusion: The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer., Competing Interests: The authors declare no competing interests., (© 2021 Zhuang et al.)
- Published
- 2021
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