Exosome Enveloped by Nano Lipid Particle a New Model for Signal Transducer and Activator of Transcription 3 Silencer Ribonucleic Acid Delivery System to a Glioblastoma Mice Model Publisher



A Monfaredan AMIR ; S Sen SENA ; A Hosseininasab ALAVIYEHSADAT ; D Tastekin DIDEM ; G Fazli GHAZALEH ; Hu Bozbey Hamza UGUR ; N Yousefi NASRIN ; M Hocaoglu MERVE ; O Oncul ORAL ; Rs Ozen Ridvan SECKIN
Source: Cancers Published:2025

Abstract

Background/Objectives: Glioblastoma is a highly aggressive brain tumor with limited treatment options and poor prognosis. Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in glioblastoma progression, making it a promising therapeutic target. However, effective delivery of STAT3-silencing agents across the blood–brain barrier remains a significant challenge. This study evaluates the efficacy of Lipid Nanoparticles-EXOSOME COMPLEX STAT3-silencer treatment in reducing glioblastoma tumor growth by facilitating efficient small interfering RNA delivery and inhibiting STAT3 expression. Methods: A novel exosome-based drug delivery system was developed using NLP-EXOSOME COMPLEX nanoparticles loaded with STAT3-silencer siRNA. The therapeutic efficacy was assessed in vitro using human glioblastoma cell lines and in vivo using a glioblastoma mouse model. Tumor progression, STAT3 expression levels, and survival rates were analyzed. Results: The results demonstrated that Lipid Nanoparticles-EXOSOME COMPLEX effectively transported STAT3-silencer siRNA into glioblastoma cells, leading to significant STAT3 downregulation. This resulted in reduced tumor proliferation, increased apoptosis, and extended survival in vivo. The combination of lipid nanoparticles and exosomes provided a stable and efficient delivery mechanism with improved uptake and therapeutic efficacy. Conclusion: Lipid Nanoparticles-EXOSOME COMPLEX STAT3-silencer treatment offers a promising approach for targeted glioblastoma therapy by overcoming the blood–brain barrier limitations and enhancing STAT3 inhibition. Further research is necessary to optimize long-term efficacy, assess potential immune responses, and explore combinatory therapeutic strategies for improved patient outcomes. © 2025 Elsevier B.V., All rights reserved.