Journal
MATERIALS HORIZONS
Volume 8, Issue 3, Pages 1017-1028Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0mh01685c
Keywords
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Funding
- Taishan Scholars Construction Engineering [tsqn20161047, tsqn201909144]
- National Natural Science Foundation of China [22007006, 31771284, 81401518, 31430028, 81630019]
- Special Project of Central Government for Local Science and Technology Development of Shandong Province [YDZX20203700001291]
- Natural Science Foundation of Anhui Province [1808085MB38]
- Shandong Provincial Natural Science Foundation [ZR2016JL026]
- Key Research and Development Plan of Shandong Province [2018GSF118230]
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The nanoplatform enhances mimic-peroxidase activity by self-supplying Cu(I), effectively inhibits tumor growth, and improves MRI contrast performance.
Theoretically, the Fenton catalytic efficiency of the Cu-based nanoplatform is approximately 160 times that of traditional Fe-based agents. However, the coordination interaction between Cu(ii) and intracellular GSH significantly inhibits the high catalytic activity of Cu(i) generation, dramatically decreasing the Fenton-like catalytic efficiency. Herein, we designed a completely new and highly efficient hierarchical structural nanoplatform to enhance the mimic-peroxidase activity through utilizing comproportionation between CuO and elemental Cu core to self-supply Cu(i). The catalytic rate of this nanoplatform was approximately 55-fold that of traditional Fe-based agents. In a cell assay, this nanoplatform could function as an antagonist of GPX4 and agonist of SOD-1, resulting in intracellular ROS and H2O2 accumulation. Next, the accumulated H2O2 could be quickly catalyzed to highly toxic OH by self-supplying Cu(i), causing strong oxidative stress damage to mitochondria and cell membranes. Under 808 nm laser irradiation, this nanoplatform exhibited a stronger inhibition of tumor growth, and effectively overcame the tumor resistance and recurrence. In addition, this hierarchical structure significantly promoted the interaction between water molecules and gadolinium centers, making TRF-mCuGd possess an ultrahigh T-1 MRI contrast performance, and hence, more pathological information of the tumor could be achieved. Overall, this work provides a promising pattern for the design and development of cancer theranostics.
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