Wang, J., Cao, M., Han, L., Shangguan, P., Liu, Y., Zhong, Y., Chen, C., Wang, G., Chen, X., Lin, M., Lu, M., Luo, Z., He, M., Sung, H. H. Y., Niu, G., Lam, J. W. Y., Shi, B., & Tang, B. Z. (2024). Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy. Journal of the American Chemical Society, 146(42), 28783-28794. https://doi.org/10.1021/jacs.4c07785
Wang, Jiefei ; Cao, Mingyue ; Han, Lulu et al. / Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy. In: Journal of the American Chemical Society. 2024 ; Vol. 146, No. 42. pp. 28783-28794.
@article{1879cab557304a36b14b3476a19ae069,
title = "Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy",
abstract = "Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood-brain barrier (BBB) permeability, and the lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4 and TriPEX-PF6) capable of BBB penetration for efficient GBM therapy via paraptosis and ferroptosis induction. These aggregation-induced emission (AIE)-active agents specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated paraptosis and GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial mitochondria-derived vacuolation, accompanied by reactive oxygen species generation, decreased mitochondrial membrane potential, and intracellular Ca2+ overload, thereby disrupting metabolisms and inducing nonapoptotic cell death. In vivo imaging revealed that TriPEX-ClO4 and TriPEX-PF6 successfully traversed the BBB to target orthotopic glioma and initiated effective synergistic therapy postintravenous injection. Our AIE drugs emerged as the pioneering paraptosis inducers against drug-resistant GBM, significantly extending survival up to 40 days compared to Temozolomide (20 days) in drug-resistant GBM-bearing mice. These compelling results open up new venues for the development of fluorescent anticancer drugs and innovative treatments for brain diseases.",
author = "Jiefei Wang and Mingyue Cao and Lulu Han and Ping Shangguan and Yisheng Liu and Yong Zhong and Chaoyue Chen and Gaoyang Wang and Xiaoyu Chen and Ming Lin and Mengya Lu and Zhengqun Luo and Mu He and Sung, {Herman H.Y.} and Guangle Niu and Lam, {Jacky W.Y.} and Bingyang Shi and Tang, {Ben Zhong}",
note = "Publisher Copyright: {\textcopyright} 2024 American Chemical Society.",
year = "2024",
month = oct,
day = "23",
doi = "10.1021/jacs.4c07785",
language = "English",
volume = "146",
pages = "28783--28794",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "42",
}
Wang, J, Cao, M, Han, L, Shangguan, P, Liu, Y, Zhong, Y, Chen, C, Wang, G, Chen, X, Lin, M, Lu, M, Luo, Z, He, M, Sung, HHY, Niu, G, Lam, JWY, Shi, B & Tang, BZ 2024, 'Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy', Journal of the American Chemical Society, vol. 146, no. 42, pp. 28783-28794. https://doi.org/10.1021/jacs.4c07785
Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy. / Wang, Jiefei; Cao, Mingyue; Han, Lulu et al.
In:
Journal of the American Chemical Society, Vol. 146, No. 42, 23.10.2024, p. 28783-28794.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy
AU - Wang, Jiefei
AU - Cao, Mingyue
AU - Han, Lulu
AU - Shangguan, Ping
AU - Liu, Yisheng
AU - Zhong, Yong
AU - Chen, Chaoyue
AU - Wang, Gaoyang
AU - Chen, Xiaoyu
AU - Lin, Ming
AU - Lu, Mengya
AU - Luo, Zhengqun
AU - He, Mu
AU - Sung, Herman H.Y.
AU - Niu, Guangle
AU - Lam, Jacky W.Y.
AU - Shi, Bingyang
AU - Tang, Ben Zhong
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/10/23
Y1 - 2024/10/23
N2 - Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood-brain barrier (BBB) permeability, and the lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4 and TriPEX-PF6) capable of BBB penetration for efficient GBM therapy via paraptosis and ferroptosis induction. These aggregation-induced emission (AIE)-active agents specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated paraptosis and GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial mitochondria-derived vacuolation, accompanied by reactive oxygen species generation, decreased mitochondrial membrane potential, and intracellular Ca2+ overload, thereby disrupting metabolisms and inducing nonapoptotic cell death. In vivo imaging revealed that TriPEX-ClO4 and TriPEX-PF6 successfully traversed the BBB to target orthotopic glioma and initiated effective synergistic therapy postintravenous injection. Our AIE drugs emerged as the pioneering paraptosis inducers against drug-resistant GBM, significantly extending survival up to 40 days compared to Temozolomide (20 days) in drug-resistant GBM-bearing mice. These compelling results open up new venues for the development of fluorescent anticancer drugs and innovative treatments for brain diseases.
AB - Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood-brain barrier (BBB) permeability, and the lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4 and TriPEX-PF6) capable of BBB penetration for efficient GBM therapy via paraptosis and ferroptosis induction. These aggregation-induced emission (AIE)-active agents specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated paraptosis and GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial mitochondria-derived vacuolation, accompanied by reactive oxygen species generation, decreased mitochondrial membrane potential, and intracellular Ca2+ overload, thereby disrupting metabolisms and inducing nonapoptotic cell death. In vivo imaging revealed that TriPEX-ClO4 and TriPEX-PF6 successfully traversed the BBB to target orthotopic glioma and initiated effective synergistic therapy postintravenous injection. Our AIE drugs emerged as the pioneering paraptosis inducers against drug-resistant GBM, significantly extending survival up to 40 days compared to Temozolomide (20 days) in drug-resistant GBM-bearing mice. These compelling results open up new venues for the development of fluorescent anticancer drugs and innovative treatments for brain diseases.
UR - http://www.scopus.com/inward/record.url?scp=85206468439&partnerID=8YFLogxK
U2 - 10.1021/jacs.4c07785
DO - 10.1021/jacs.4c07785
M3 - Article
C2 - 39394087
AN - SCOPUS:85206468439
SN - 0002-7863
VL - 146
SP - 28783
EP - 28794
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 42
ER -
Wang J, Cao M, Han L, Shangguan P, Liu Y, Zhong Y et al. Blood-Brain Barrier-Penetrative Fluorescent Anticancer Agents Triggering Paraptosis and Ferroptosis for Glioblastoma Therapy. Journal of the American Chemical Society. 2024 Oct 23;146(42):28783-28794. doi: 10.1021/jacs.4c07785