Ferroptosis, a newly programmed cell death paradigm, is expected to provide a new opportunity for the safe and efficient theranostic of glioma. However, the current ferroptosis agents lack effective in vivo tracer function and only have low specific activation efficiency. NIR-Ⅱ (1000-1700 nm) aggregation-induced emission (AIE)-based in vivo fluorescence imaging has the advantages of deep-penetration, aggregation-enhanced emission, high signal-to-noise ratio, and real-time imaging. It is an advanced technique for monitoring the in vivo metabolism and distribution of nano-drugs. Based on the merits of AIE and the feature of glioma, we developed a brain-targeted ferroptosis agent with NIR-Ⅱ fluorescence imaging and Au (I) active center for highly specific ferroptosis for the first time. The system not only effectively monitored the BBB penetration and in vivo distribution of nano-drugs, but also specifically activated the TrxR-HMOX1-mediated ferroptosis pathway by targeting the thioredoxin reductase (TrxR) that is highly expressed in glioma. After effective inhibition of GBM, it greatly prolonged the survival of glioma-bearing mice. This study provides an important reference for the development of next-generation advanced visual nanodrugs.
The research results was published entitled as “A Brain-Targeting NIR-II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma" in Advanced Science (IF=17.521). Prof. Jing Zhang from SMU and master student Lulu Han from HENU are co-first authors. Prof. Benzhong Tang, Prof. Bingyang Shi, Associate Prof. Jiefei Wang and Prof. Lei Zheng areco-corresponding authors.
Henan Key Laboratory of Brain Targeted Bio-nanomedicine is supported by the College of Life Science and the College of Pharmacy, Henan University. In September 2015, the laboratory was established as HENU-MQ Joint Center of Biomedical Innovation, and was subsequently approved as Nano Biomedical International Joint Laboratory of Henan Province in 2016, Bio-Nano Medicine Disciplinary Innovation and Talent Introduction Center of Henan Province in 2018. It was then designated as a Key Laboratory of Henan Province in 2020 after receiving approval from the Department of Science and Technology.
The lab's work concentrates on understanding the mechanisms behind brain disorders, creating novel diagnostic and therapeutic approaches. A series of research results have been achieved in developing targeted therapies for brain disorders, investigating new therapeutic targets and delivery mechanisms, development and application of brain diagnosis and treatment system, brain delivery system Construction, preclinical evaluation and translation of brain-targeted nanomedicines. This has effectively supported the construction of " First-Class Discipline" - biology of HENU, promoting the integration of biology and related disciplines and the development of " Biology plus".
Paper link：https://doi.org/10.1002/advs.202206333
