1. PDGF receptor-β-targeted copper-gadolinium-oxide self-assembled nanoclusters suppress tumor growth and metastasis via copper overload-mediated apoptosis and anti-angiogenesis.
- Author
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Yan, Miao, Qi, Xiangyu, Xie, Wenteng, Xiao, Jianmin, Gan, Yuehao, Wang, Peng, Zhang, Caiyun, Xu, Zhaowei, Zhang, Jia, Tian, Geng, Wu, Zhengyan, and Zhang, Guilong
- Subjects
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TUMOR growth , *COPPER , *PLATELET-derived growth factor receptors , *METASTASIS , *CELL migration , *APOPTOSIS - Abstract
• A novel PDGFB-conjugated copper-gadolinium oxide nanocluster (PDGFB-CGO) was fabricated. • PDGFB-CGO could positively recognize tumor tissue and was effectively internalized within the cancer cells. • PDGFB-CGO showed effective synergistic action of CDT and PTT. • PDGFB-CGO suppressed EMT and tumor angiogenesis, thereby restricting tumor cell migration and invasion. • PDGFB-CGO disrupted the intracellular copper balance, thereby inducing tumor cell apoptosis and anti-angiogenesis. The major hurdles for cancer therapy include controlling tumor growth and metastasis. Herein, we developed a novel platelet-derived growth factor receptor - β (PDGFR - β)-recognizing cyclic peptide (PDGFB)-conjugated copper-gadolinium oxide (CGO) nanocluster (PDGFB-CGO) to suppress tumor growth and metastasis via copper overload-mediated apoptosis and anti-angiogenesis. The developed PDGFB-CGO showed not only ultra-strong Fenton-catalytic activity and PT performance but also excellent T 1 contrast ability. It effectively recognized the tumor tissue, thereby significantly improving its tumor-specific delivery and upon laser irradiation, quickly ablated tumor cells contributing to PTT. In addition, PDGFB-CGO quickly produced abundance of highly active Cu(I) which catalyzed endogenous hydrogen peroxide (H 2 O 2) into hydroxyl radical (·OH), achieving ultra-high cancer CDT efficiency. In addition, the influx of Cu(I) broke copper homeostasis, thereby suppressing epithelial-mesenchymal transition (EMT) and tumor angiogenesis. This process restricted cell migration and invasion, which dramatically blocked cancer metastasis. In addition, the systemic delivery of PDGFB-CGO significantly enhanced the MRI signal in the tumor, which would be beneficial for the accurate diagnosis of cancer. Thus, this work provides a promising strategy to develop advanced biomaterials for efficient theranostic applications in cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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