Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a common tumor suppressor gene that plays an important role in the initiation and progression of glioblastoma (GBM). Loss of PTEN activity in GBM patients is associated with treatment resistance, tumorigenesis, and poor prognosis. Messenger RNA (mRNA) has recently shown promise in treating various brain diseases. However, the properties of mRNA (e.g., instability, poor targeting, inability to cross the blood-brain barrier, etc.) seriously hinder the application of mRNA in GBM. To solve these problems, our laboratory designed a new mRNA nanomedicine (ABNPs@mRNA), which can effectively solve the current challenges of mRNA. The new mRA nanomedicinehas the following characteristics:
(1) The modification of ApoE peptide can greatly improve the accumulation of drugs in the brain tumor.
(2) Biomimetic strategies based on cell membranes can effectively achieve immune escape in the body.
(3) The characteristics of tumor microenvironment response can promote the efficient release of mRNA in the tumor site. The biomimetic nanomedicine had good therapeutic effect in U87MG and CSC2 GBM stem cell in situ tumor-bearing mouse models, which could significantly inhibit tumor growth and prolong the survival time of mice without obvious toxic side effects. This biomimetic nanomedicine provides new ideas for gene therapy of GBM.
The research results was published entitled as “Non-invasive PTEN mRNA brain delivery effectively mitigates growth of orthotopic glioblastoma” in Nano Today (IF=18.962). Dr. Yanjie Liu and Ph.D. candidate Dongya Zhang shared the first authors. Prof. Bingyang Shi, Prof. Yan Zou and Prof. Meng Zheng shared the co-corresponding authors.
Paper link：https://doi.org/10.1016/j.nantod.2023.101790
