Advanced Materials: The navy team of the Shanghai Institute of Medicine developed an acid-activated drug delivery system to induce iron death of tumor cells and enhance anti-tumor immune response

Immunotherapy can activate the systemic anti-tumor immune effect, inhibit tumor growth, metastasis and recurrence, and has shown great potential in clinical tumor treatment

Iron death is a new type of cell death caused by iron-dependent lipid peroxidation discovered in recent years

At the same time, iron death-related lipid peroxides can be used as a "discover me" signal to promote the recognition, phagocytosis and processing of tumor antigens by dendritic cells, and present tumor-associated antigens to CD8+ T lymphocytes, thereby activating cells Toxic T lymphocytes enhance tumor immunotherapy

Based on the above research background, the Haijun Yu team of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences 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

Related research results will be published in Advanced Materials journal on June 25, 2021

Researchers first designed and synthesized an amphiphilic acid-sensitive polymer block copolymer coupled with photosensitizer pyropheophorbide (PPa) and phenylboronic acid, which contained poor solubility through hydrophobic interaction and π-π conjugation.

Research data shows that the nanoparticles encapsulating RSL-3 can be selectively enriched in tumor tissues through the EPR effect, and the application of external light can induce the immunogenic death of tumor cells, initiate anti-tumor immune responses, and induce the secretion of cytotoxic T lymphocytes.

More importantly, IFN-γ and RSL-3 can block the cystine-glutamate transport receptor-glutathione peroxidase (SystemXc--GPX4)-mediated lipid peroxide repair pathway, respectively , Increase the accumulation of lipid peroxide in tumor cells

Schematic diagram of acid-activated nanoparticles for inducing iron death of tumor cells and enhancing anti-tumor immunotherapy

This immune curative effect strategy based on tumor cell iron death is expected to provide new ideas for improving iron death-mediated tumor immunotherapy

Song Rundi, a graduate student of Shanghai Institute of Materia Medica, and Li Tianliang, a postdoctoral fellow, are the co-first authors of this study, and researcher Yu Haijun is the corresponding author of this article

Original source:

Rundi Song, Tianliang Li, Jiayi Ye, et al.