PDGF receptor-?-targeted copper-gadolinium-oxide self-assembled nanoclusters suppress tumor growth and metastasis via copper overload-mediated 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-beta (PDGFR-beta)-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 T1 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 (H2O2) 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.