Development of Innovative and Actively Targetable Non-Viral Gene Delivery Systems for Tumor Suppressor Gene Induction and Investigation of Their Anti-Tumor Activity
Project no. 32183 · Status: Kapanmış (Yayın bekleniyor) · 2024
Summary
<p>Glioblastoma multiforme (GBM) remains a devastating and largely untreatable brain cancer due to its aggressive growth and resistance to conventional therapies. The frequent loss or mutation of the PTEN tumor suppressor gene plays a critical role in GBM progression, emphasizing the urgent need for innovative therapeutic strategies. In this study, we developed and validated a microfluidics-based lipid nanoparticle (LNP) system specifically designed to enhance PTEN expression in GBM cells. Unlike conventional nanoparticle synthesis methods, our microfluidic platform enables precise control over particle size, composition, and encapsulation efficiency, yielding highly uniform and reproducible LNPs. To achieve targeted delivery, the LNPs were functionalized with the tumor-penetrating peptide iRGD, which selectively binds to αv integrins overexpressed in GBM cells. This dual innovation—a microfluidic platform for advanced LNP synthesis and iRGD-mediated tumor targeting—sets our strategy apart in the field of gene therapy. The iRGD-conjugated LNPs (LNP-iRGD) induced a robust increase in PTEN expression within GBM cells, triggering apoptosis, reducing proliferation, and sparing healthy cells. Additionally, the microfluidic synthesis ensured scalable production of LNPs with superior stability and protection of pDNA-PTEN against enzymatic degradation. These findings establish our microfluidic LNP-iRGD system as a transformative advancement in targeted gene therapy for GBM. By combining precision engineering and molecular targeting, this approach represents a breakthrough in precision oncology with the potential for broad applicability across other malignancies.</p>