Schematic diagram of acid-activated nanoparticles used to induce iron death of tumor cells and enhance anti-tumor immunotherapy.
Schematicdiagram of acid-activated nanoparticles used to induce tumor cell iron death and enhance anti-tumor immunotherapy Schematic diagram of acid-activated nanoparticles used to induce tumor cell iron death and enhance anti-tumor immunotherapy Kill a thousand enemies and hurt yourself eight hundred
There are often such scenes in wars.
In real life, tumor immunotherapy also faces a similar dilemma
Recently, the team of Yu Haijun, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, gave a solution
"Cunning" cancer cells
"Cunning" cancer cells Immunotherapy can activate the systemic anti-tumor immune effect, inhibit tumor growth, metastasis and recurrence, and has shown great potential in clinical tumor treatment
"The main reason is that tumor cells usually show low immunogenicity, and T lymphocytes cannot recognize tumor cells
Yu Haijun explained that, generally speaking, if human cells become abnormal, the immune system should be able to eliminate them
"We hope that the immune system can recognize and remove tumor cells, but tumor cells are relatively low in immunogenicity.
"Immune checkpoint antibody drugs can activate the immune effect of some cancer patients and significantly prolong the survival time of cancer patients
Therefore, how to eliminate tumor immune tolerance, improve the clinical response rate of immune checkpoint antibody drugs, and reduce their toxic side effects has become a major basis and clinical problem for improving immune checkpoint therapy
One "positive" one "negative" regulation
One "positive" one "negative" regulation "The so-called'positive regulation' is to activate our immune system, strengthen our immunity, and produce a protective effect, thereby eliminating some foreign things (such as viruses, bacteria, etc.
"Sometimes, negative regulation is also helpful to human health
Iron death is a new type of cell death caused by iron-dependent lipid peroxidation discovered in recent years
"The inactivation of glutathione peroxidase and antiporter will block the reverse transport of intracellular glutamate and extracellular cystine, inhibit intracellular glutathione synthesis, and cause lipid peroxides.
Based on this, the Yu Haijun team proposed a strategy to use the acid-sensitive drug delivery system to synergistically induce tumor cell iron death and immunogenic death, thereby improving the anti-tumor immune response
.
Researchers have designed and synthesized an amphiphilic acid-sensitive polymer block copolymer coupled with photosensitizers pyropheophorbide and phenylboronic acid, which contains insoluble small molecule iron death inducers through hydrophobic interaction and conjugation.
RSL-3
.
Yu Haijun said: "Using the acid-sensitive drug delivery system, on the one hand, it can activate protective immunity, on the other hand, it can also inhibit the negative regulatory effect of cancer cells on immunity, so as to achieve a more ideal therapeutic effect
.
"
"Half survival time" tripled
"Half survival time" tripled Studies have shown that nanoparticles containing the small molecule iron death inducer RSL-3 can be selectively enriched in tumor tissues through enhanced tumor penetration and accumulation effects.
The application of external light can induce tumor cell immunogenic death and initiate anti-tumor activity.
Immune response
.
More importantly, this process can mediate the lipid peroxide repair pathway and increase the accumulation of lipid peroxide in tumor cells
.
Due to the synergistic induction of iron death, the infiltration of dedifferentiated tumor cells in tumor tissues was reduced by 4 times after treatment
.
After further treatment with immune checkpoints, the infiltration of cytotoxic T lymphocytes in tumor tissues increased by 4 times, effectively inhibiting tumor growth and metastasis, and improving the survival rate of tumor-bearing mice
.
In the experiment, the researchers calculated based on data and found that the half-life of tumor-bearing mice (the survival rate of tumor-bearing mice is 50% of the survival time) increased by more than two times
.
Haijun Yu’s team has conducted long-term research in the field of tumor immunotherapy.
The team has also developed a tumor microenvironment-activated immune checkpoint antibody drug delivery system.
The related research was published in "Science-Immunology"
.
"Immunotherapy is a new method of anti-tumor clinical treatment that has been given high expectations by patients and clinical experts in addition to surgery, chemotherapy, and radiotherapy
.
Unfortunately, even the best antibody drugs are targeted at various types of patients, including lung cancer patients.
The 5-year clinical survival rate of advanced solid tumors has never exceeded 30%
.
How to improve the 5-year clinical survival rate of immune checkpoint antibody therapy is still a major scientific and clinical problem we face
.
" said Li Bin, a distinguished professor of Shanghai Jiaotong University.
"This immune curative effect strategy based on iron death of tumor cells is expected to provide new ideas for improving iron death-mediated tumor immunotherapy
.
" (Source: China Science News Zhang Shuanghu)
Related paper information: https://doi.
org/10.
1002/adma.
202101155
https://doi.
org/10.
1002/adma.
202101155
This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only.
This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of
the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed
description of the concern or complaint, to
service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content
will be removed immediately.
