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Shen Qi’s Team Made Progress in Ferroptosis Combinational Anti-Cancer Therapy

June 09, 2021      Author:

Ferroptosis is a recently recognized form of apoptotic cell death, which has great potential in anti-tumor therapy and plays an important role in the appearance, development and metastasis of tumor. Shen Qi’s research team from the School of Pharmacy of Shanghai Jiao Tong University studied the mechanism of ferroptosis and designed a novel nanodrug delivery system. The team explored the mechanism and effect of ferroptosis/pyroptosis combinational anti-cancer therapy as well as ferroptosis combined with immunotherapy.

Shen Qi’s team designed a dual-inductive nano- system, which can result in excessive ROS in tumors and initiate ferroptosis/pyroptosis dual-inductive antitumor immunity. The in vivo experiments demonstrated that this nanodrug (Tf-LipoMof @ PL) has a good anti-tumor effect, and it further validated that the ferroptosis/pyroptosis dual-induction nano-system blazes a new path for tumor treatment.

 

Immunotherapy is also a hot topic in oncotherapy. Shen Qi’s research team designed a multi-functional nanodrug delivery system to investigate the mechanism and anti-tumor effect of ferroptosis combined with immunotherapy. The smart biomimetic nanoplatform integrates tumor metabolism and immunity based on ROS-ferroptosis-glycolysis regulation, providing a potential anti-tumor strategy.

Related findings were recently published in Nanoscale Horizons (2020, 10, 2272-2298.) first-authored by Xu Rui, a master student in Shen Qi’s research team; and Journal of controlled release (2021, 334, 21-33), first-authored by SJTU PhD student Yang Jie. Shen Qi is the corresponding author. This research was funded by the National Natural Science Foundation of China (81972812) and the Shanghai Jiao Tong University Young Teacher Initiation Program (20x100040060).

Author: Shen Qi’s research team

SourceSchool of Pharmacy, SJTU

Translated by Zhang Yue

Proofread by Xiao Yangning, Fu Yuhe

 

 

 

Ferroptosis/pyroptosis dual-inductive combinational anti-cancer therapy achieved by transferrin decorated nanoMOF

ABSTRACT:

Non-apoptotic cell death such as ferroptosis and pyroptosis has shed new light on cancer treatment, whereas combinational therapy using both these mechanisms has not yet been fully explored. Herein, a dual-inductive nano-system to realize ferroptosis/pyroptosis mediated anti-cancer effects is presented. The nanodrug (Tf-LipoMof@PL) is constructed with a piperlongumine (PL) loaded metal–organic framework (MOF) coated with transferrin decorated pH sensitive lipid layer. Intracellular iron was enriched with an iron-containing MOF, whose endocytosis can be further facilitated by transferrin decorated on the lipid layer, which provides a prerequisite for the occurrence of ferroptosis and pyroptosis. Piperlongumine as the ferroptosis inducer can strengthen the ferroptotic cell death, and provide H2O2 for the dual induction system to increase ROS generation through Fenton reaction. On the basis of validation of both ferroptosis and pyroptosis, the dual-inductive nanodrug demonstrated ideal anticancer effects in the xenograft mice model, which proved that the ferroptosis/pyroptosis dual-inductive nanoplatform could be an effective and promising anticancer modality.

 

Smart biomimetic metal organic frameworks based on ROS-ferroptosis-glycolysis regulation for enhanced tumor chemo-immunotherapy

ABSTRACT:

Antitumor immunotherapy is limited by low tumor immunogenicity and immunosuppressive microenvironment (TIME), which could be improved by “ROS-ferroptosis-glycolysis regulation” strategy. Herein, a cancer cell membrane coated metal organic framework (MOF) loading with glucose oxidase (GOx) and doxorubicin (DOX) was constructed (denoted as mFe(SS)/DG). Benefiting from the homotypic targeting of cancer cell membrane, the nanoplatform effectively accumulated in tumors. mFe(SS)/DG based on coordination between Fe3+ and disulfide-bearing ligand scavenged GSH and downregulated glutathione peroxide 4 (GPX4) to trigger ferroptosis. GOx catalyzed glucose to generate abundant H2O2 for enhancing Fenton reaction, resulting in excessive ROS in tumors. The ROS burst simultaneously promoted ferroptosis and inhibited glycolysis. Ferroptosis combined with DOX induced immunogenic cell death (ICD) and released tumor antigens to initiate antitumor immunity. Glycolysis repression remodeled TIME by decreasing lactate to solidify and boost the antitumor immunity. The smart biomimetic nanoplatform integrates tumor metabolism and immunity based on ROS-ferroptosis-glycolysis regulation, providing a potential anti-tumor strategy.