A research team at Severance Hospital has developed a cell membrane-derived nanoparticle (CMNP) capable of preserving the larynx in laryngeal cancer.
The hospital said that intercellular interactions help cell growth, differentiation, and tissue regeneration and affect cancer development and metastasis. Therefore, CMNP is a major research topic in regenerative medicine as a substance involved in cell-cell interactions. However, while there have been many studies analyzing the material characteristics of CMNP, few studies have revealed the relationship between cells and CMNP.
To provide answers, the team, led by Professor Sung Hak-joon of the Department of Medical Engineering at Yonsei University College of Medicine, has developed a CMNP that minimizes side effects, including cancer occurrence, while leaving positive effects, such as cell growth and tissue regeneration, intact, and confirmed its therapeutic effect in laryngeal cancer.
“In laryngeal cancer, hospitals remove the larynx through surgery, making it necessary to regenerate cartilage such as the shield cartilage and thyroid cartilage surrounding the larynx after surgery,” Professor Sung said. “At this stage, intercellular interactions through CMNPs are essential for cartilage regeneration.”
The research team treated laryngeal cancer cells and bone marrow-derived stem cells with CMNP and cultured them to reveal the role of CMNP in increasing cell-to-cell interactions, Sung added.
In the case of treatment with CMNP in which the protein that improves adhesion between cells was preserved, the team confirmed that the adhesion between cells increased by 1.5 times compared to the control group, thus promoting cartilage differentiation through cell regeneration and differentiation.
“However, the expression of cancer-causing hypoxia-inducing factor increased 1.8 times,” Professor Sung said. “The team confirmed that a higher expression of hypoxia inducing factor increased cancer cells growth.”
To reduce cancer cell growth, the research team has developed a new cell membrane-derived nanoparticle (CMNP_PEG_apt) that prevents cancer growth and metastasis.
“Our team conjugated an aptamer that inhibits Notch 1 signaling to CMNP to induce cancer cell death,” Sung said. “The Notch 1 signal promotes cancer growth by creating new blood vessels and inhibits cartilage differentiation by interfering with collagen production in the early stages of cartilage development.”
To confirm the anticancer effect of the new nanoparticles, the team treated laryngeal cancer cells with nanoparticles for three days. It then analyzed the gene expression related to cancer cell death by a real-time gene amplification test.
As a result of the study, the researchers confirmed that the group treated with nanoparticles had a 4.9 times higher expression of a gene that kills cancer cells than that in the control group.
Also, the cartilage regeneration effect of the developed treatment was high.
“The research team analyzed the amount of extracellular matrix generated during cartilage differentiation by injecting nanoparticles into bone marrow mesenchymal stem cell (BMSC) pellets for 21 days,” Sung said. “We confirmed that the extracellular matrix production was 5.7 times higher in the group treated with nanoparticles than in the control group.”
The research team also confirmed the potential of the nanoparticles to treat laryngeal cancer through an experiment on mice expressing laryngeal cancer.
As a result of observation for 28 days, the size of cancer in the group of mice injected with nanoparticles was about 1.8 times smaller than that of the control group.
“Until now, there was a limit to CMNP research to molecular biological research that reveals the properties of the substance itself, but this research will help expand the research field to the relationship and structure of cells and CMNPs,” Sung said. “As the team confirmed that the nanomaterial conjugated with the aptamer that inhibits the Notch 1 signal inhibits cancer growth, we expect that we will be able to apply it to various cancers as well as laryngeal cancer.”
The results of the research were published in the latest issue of Advanced Materials.