Chemical Engineering of Extracellular Vesicles for Enhanced Glioblastoma Therapy: Undergraduate Biomedical Research at Southern Utah University

Glioblastoma, a highly aggressive brain cancer with a mere 15-month survival rate, impacts over 15,000 individuals annually in the US, inflicting considerable financial strain and a morbidity rate surpassing 30%. Traditional treatments such as surgery, radiation, and the chemotherapy drug temozolomide often yield restricted remission due to barriers posed by tumor inaccessibility, microenvironment intricacies, and drug resistance, leading to significant side effects. Overcoming these challenges requires innovative approaches. A promising avenue involves harnessing nanosized extracellular vesicles (EVs) for drug delivery. EVs, with their inherent involvement in cellular communication, offer an enticing solution. Their biological origin circumvents issues of immunogenicity, toxicity, and clearance frequently encountered by synthetic nanoparticle systems. EVs are readily isolable from bodily fluids across species, finding abundant availability in bovine milk. By leveraging EVs' natural functions, including enhanced targetability and cellular communication, the potential for successful therapy delivery increases substantially. Incorporating specific targeting moieties, such as the cytolytic peptide Pep-1-Phor21, enhances EV efficacy; this peptide targets the overexpressed Interleukin-13 Receptor α2 on glioblastoma cells. This synergistic coupling of Pep-1-Phor21 and bovine milk-derived EVs promises a more effective targeted delivery of encapsulated chemotherapeutics such as temozolomide. Our hypothesis is that bovine milk-derived EVs can be engineered with Pep-1-Phor21 and encapsulated temozolomide to enhance the demise of glioblastoma cells. This proposal outlines three aims: 1) determine the capability of Pep-1-Phor21-modified bovine milk-derived EVs to cross the blood-brain barrier; 2) evaluate the efficacy of Pep-1-Phor21-modified EVs loaded with temozolomide in delivering their payload to glioblastoma cells; and 3) determine the optimal dosage and internalization route of Pep-1-Phor21-temozolomide EVs in vitro. This work not only demonstrates the adaptability of bovine milk EVs but also advances EV-based drug delivery, ultimately enriching the landscape of glioblastoma treatment options. Project Number: 1R16GM154694-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Jessica Pullan | Institution: UTAH STATE HIGHER EDUCATION SYSTEM--SOUTHERN UTAH UNIVERSITY, CEDAR CITY, UT | Award Amount: $155,695 | Activity Code: R16 | Study Section: Special Emphasis Panel[ZGM1 RCB-X (SU)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11097642