Researchers from Tel Aviv University have proven that a lipid nanoparticle-based drug delivery system can use RNA to overcome resistance to both chemotherapy and immunotherapy in cancer treatments. cancer. The study opens a new path towards a personalized and targeted fight against cancer. The results were published in the scientific journal Advanced materials.
The study was led by TAU Vice President for R&D, Professor Dan Peer, Head of the Precision Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research, Wise Faculty of Life Sciences. life and fellow of the Roman Abramovich Center for Nanoscience and Nanotechnology. , in collaboration with postdoctoral researcher Dr Seok-Beom Yong from South Korea. The study was funded by an ERC grant from the European Union and a research grant from the Korean government.
Chemoimmunotherapy, which combines chemotherapy with immunotherapy, is considered the most advanced standard of care for various types of cancer. While chemotherapy destroys cancer cells, immunotherapy encourages immune system cells to identify and attack the remaining cancer cells. However, many patients do not respond to chemoimmunotherapy, which means that the treatment is not targeted enough. Professor Peer and his team are the first in the world to prove the feasibility of a drug delivery system based on lipid nanoparticles that release their charge only at specifically targeted cells – cancer cells for chemotherapy and cells immune systems for immunotherapy.
“In our system, a single nanoparticle is able to operate in two different domains,” explains Professor Peer. “It increases the susceptibility of chemo-resistant cancer cells, while invigorating immune cells and increasing their susceptibility to cancer cells. So, with a precisely targeted nanoparticle, we are providing two different treatments, at very different sites. We have tested this system in two types of laboratory models — one for metastasized melanoma, and the other for a local solid tumor.In both populations we observed positive effects of our delivery system.
The new development from Professor Peer’s team builds on another recent discovery: an enzyme called HO1 is used by cancer cells both to resist chemotherapy and to hide from the immune system. Silencing HO1 in the tumor is therefore considered an optimal strategy in clinical research, but so far all attempts to silence the enzyme have resulted in serious side effects.
“Chemoresistant tumors represent a significant challenge in our never-ending fight against cancer,” says Professor Peer. “Our goal is to silence the HO1 enzyme that allows tumors to develop resistance to chemotherapy and hide from the immune system. But existing methods for silencing HO1 resemble using an F-16 fighter jet to blow up a tiny ant. Our new nanomedicine knows how to precisely target cancer cells, silence the enzyme and expose the tumor to chemotherapy, without damaging surrounding healthy cells.Then the same nanoparticle travels to immune system T cells and reprograms them to identify cancer Active and very aggressive tumors are able to hide from the immune system, and we restore the ability of immune cells to recognize cancer as a foreign body and attack it.
“This is the first example of a single drug based on an RNA-loaded nanoparticle performing two very different, if not opposing, tasks,” adds Professor Peer. “This is only an initial study, but it has enormous potential in the ongoing fight against cancer.”
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Materials provided by Tel Aviv University. Note: Content may be edited for style and length.
