A Brain‐Targeting NIR‐II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma

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Abstract
Near‐infrared‐II (NIR‐II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron‐based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)‐based NIR‐II ferroptosis nanoparticles (TBTP‐Au NPs) for brain‐targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real‐time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP‐Au specifically activates the effective heme oxygenase‐1‐regulated ferroptosis of glioma cells to greatly extend the survival time of glioma‐bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high‐specificity visual anticancer drugs for clinical trials.
Funding Information
  • National Natural Science Foundation of China (22275050, 22205096, 32001071, 32071388)
  • National Postdoctoral Program for Innovative Talents (BX20180091)
  • China Postdoctoral Science Foundation (2018M640671)
  • Southern Medical University (2021J002)

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