March 1, 2024

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New progress in the study of iron death combined with multiple treatments

New progress in the study of iron death combined with multiple treatments

 

New progress in the study of iron death combined with multiple treatments.   Cancer is a very dangerous disease. Due to its high degree of malignancy and poor prognosis, it greatly threatens human health and has become a major problem that needs to be solved urgently.

At present, most conventional chemotherapeutic drugs and targeted drugs inhibit tumor progression by inducing apoptosis. The study of new non-apoptosis-related death modes provides new ideas for cancer treatment. Iron death is a new type of programmed cell death discovered in recent years. It plays an important role in tumor occurrence, development and metastasis. Iron death has huge potential advantages for anti-tumor therapy.

In order to further improve the anti-tumor effect of iron death, it is of great significance to study the mechanism of iron death and combine with other treatment methods to develop a multi-functional intelligent treatment system.

Recently, Shen Qi’s research group from the School of Pharmacy of Shanghai Jiaotong University has thoroughly studied the mechanism of iron death, innovatively designed a nano-drug delivery system, and explored the anti-tumor mechanism and effect of iron death and scorch death, iron death and immune combined therapy.

Since the potential of the combined therapy of iron death and pyrolysis has not been fully studied in cancer treatment, Shen Qi’s research group designed a dual-induction nano-delivery system to achieve dual-mediated iron death/pyrolysis by causing intracellular iron-induced ROS to increase. The anti-cancer effect.

A dual-induction nano-delivery system was designed to achieve the dual-mediated anticancer effect of iron death/pyrolysis by causing intracellular iron-induced ROS increase. The nano-delivery system (Tf-LipoMof @ PL) is composed of a metal-organic framework (MOF) encapsulated in a pH-sensitive lipid layer mediated by transferrin, and piperamide is encapsulated in the MOF. MOF containing iron can be used as an effective iron donor after being swallowed by cells.

The transferrin decorated on the lipid layer can not only promote the endocytosis of nanoparticles through targeting, but also promote the absorption and circulation of intracellular iron, and further promote the accumulation of intracellular iron, which is the occurrence of iron death and pyrolysis. Prerequisites are provided.

Piper amide as a H2O2 donor further promoted the iron-dependent Fenton reaction and generated a large amount of ROS. The results show that Tf-LipoMof @ PL can significantly increase the levels of intracellular iron and ROS, and shows the dual induction effect of iron death and pyrolysis.

The in vivo experiments of this study also proved that Tf-LipoMof @ PL has a good anti-tumor effect, further verifying that the iron death/pyrodegeneration dual-sensing nanosystem can be used as an effective anti-tumor method.

 


Immunotherapy is currently a hot spot in the field of tumor therapy. Shen Qi’s research group designed a multifunctional nano-drug delivery system to explore the mechanism and anti-tumor effects of iron death combined immunotherapy. The low tumor immunogenicity and immunosuppressive microenvironment limit the effect of anti-tumor immunotherapy. Aiming at this problem, Shen Qi’s research group constructed a nano metal organic framework containing glucose oxidase (GOx) and adriamycin wrapped in cancer cell membranes ( Expressed as mFe(SS)/DG). Thanks to the tumor homologous targeting effect of the cancer cell membrane, the nano drug delivery system effectively accumulates at the tumor site.

Fe3+ in the mFe(SS)/DG structure and organic ligands with disulfide bonds effectively eliminate GSH in tumors and down-regulate glutathione peroxide 4 (GPX4) to induce iron death. GOx catalyzes the production of a large amount of H2O2 from glucose to enhance the Fenton reaction, leading to the accumulation of ROS in the tumor, which in turn promotes iron death and inhibits glycolysis.

The combination of iron death and doxorubicin can induce immunogenic cell death, release tumor antigens, enhance tumor immunogenicity and initiate anti-tumor immunity. The nano-drug delivery system reduces the lactic acid in the tumor site by inhibiting glycolysis, thereby weakening the immunosuppression caused by excessive lactic acid in the tumor site, and reshaping the immune microenvironment to enhance anti-tumor immunity.


The intelligent bionic nano-nano drug delivery system is based on ROS-iron death-glycolysis to regulate tumor metabolism, induce iron death and combine immunotherapy, providing a new strategy for iron death-based anti-tumor therapy.

 

 

(source:internet, reference only)


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