Platinum nanoparticles promote breast cancer cell metastasis by disrupting endothelial barrier and inducing intravasation and extravasation
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Ji-Min Cao1(
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Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype. Recently, nanomedicine becomes a promising therapeutic strategy for breast cancer, such as platinum nanoparticles (PtNPs). Despite the promising anticancer effects of PtNPs, the safety of PtNPs remains to be fully evaluated. Herein, a series of cell and animal experiments demonstrate that PtNPs facilitate breast cancer metastasis by damaging the vascular endothelial barrier. PtNPs disrupt endothelial cell proliferation, migration and tube-like structure formation, destruct endothelial adhesions junctions and induce endothelial barrier leakinessin vitro most likely by stimulating intracellular reactive oxygen species (ROS) generation and altering the expression and conformation of endothelial junctional proteins, thus promoting intravasation and extravasation of the implanted 4T1 breast cancer cells and leading to cancer metastasis in female BALB/c nude micein vivo. In addition, smaller PtNPs (5 nm) are more potent than larger PtNPs (70 nm) in exerting the above effects. The study provides the first evidence that PtNPs can promote breast cancer metastasis by damaging endothelial barrier. The unexpected detrimental effects of PtNPs should be considered in future nanomedicine designs for the treatment of breast cancer.
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Platinum nanoparticles promote breast cancer cell metastasis by disrupting endothelial barrier and inducing intravasation and extravasation
), Ji-Min Cao1(
)
Abstract
Breast cancer is a common malignancy in women with disappointing prognosis especially the triple-negative subtype. Recently, nanomedicine becomes a promising therapeutic strategy for breast cancer, such as platinum nanoparticles (PtNPs). Despite the promising anticancer effects of PtNPs, the safety of PtNPs remains to be fully evaluated. Herein, a series of cell and animal experiments demonstrate that PtNPs facilitate breast cancer metastasis by damaging the vascular endothelial barrier. PtNPs disrupt endothelial cell proliferation, migration and tube-like structure formation, destruct endothelial adhesions junctions and induce endothelial barrier leakinessin vitro most likely by stimulating intracellular reactive oxygen species (ROS) generation and altering the expression and conformation of endothelial junctional proteins, thus promoting intravasation and extravasation of the implanted 4T1 breast cancer cells and leading to cancer metastasis in female BALB/c nude micein vivo. In addition, smaller PtNPs (5 nm) are more potent than larger PtNPs (70 nm) in exerting the above effects. The study provides the first evidence that PtNPs can promote breast cancer metastasis by damaging endothelial barrier. The unexpected detrimental effects of PtNPs should be considered in future nanomedicine designs for the treatment of breast cancer.
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Acknowledgements
This study was supported by the Key Medical Science and Technology Program of Shanxi Province (No. 2020XM01), Shanxi “1331” Project Quality and Efficiency Improvement Plan (No. 1331KFC), Applied Basic Research Program of Shanxi Province (Nos. 201801D221408 and 201901D211320), Supporting Project for Returned Overseas Researchers of Shanxi Province (No. 2020-081), and partially by the National Natural Science Foundation of China (Nos. 81801858, 22007063, and 82170523). The authors thank the Core Facility Center of Shanxi Medical University for providing TEM, flow cytometry and other technical services.
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