Date of Award

Spring 2026

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2026

Department

Bioengineering

First Advisor

Bill Lu

Abstract

Treatments for glioblastoma (GBM) are limited, mainly because the blood-brain barrier (BBB) prevents large molecules like chemotherapeutic drugs from reaching brain cells, and other methods like brain surgery are incredibly invasive. Brain surgery is useful for large masses of tumors, but the surgery can’t always remove the entire tumor, which is where radiation can be used, but only in limited quantities to prevent neural damage. To circumvent these gaps in modern medicine, exosomes, which are naturally secreted nanoparticles, offer an exciting way to deliver treatments to diseased cells. Exosomes biologically cross the BBB and transport materials between cells. In our project, we took advantage of this pre-existing system and designed a series of genetic constructs that, when expressed on the exosome surface, can be used to specifically target brain cancer cells. To do this, we uniquely designed a dual-targeting mechanism. Rather than just using one targeting moiety, we identified EGFRvIII and RGD-binding integrins as two peptides overexpressed on glioblastoma cell surfaces, and the dual-targeting nature of our constructs will reduce off-target effects and increase specificity of our exosomes to GBM cells. To test the stability of our genetic construct designs in cellular systems, we transfected our construct into human 293T cells with polyethylenimine (PEI), studied their integration using confocal microscopy and exosome harvesting, and confirmed their functional presence through a luciferase assay. Through both our imaging and biochemical assay results, we can conclude that our genetic constructs are able to integrate onto exosome membrane surfaces and be expressed readily. Our dual-targeting nanovesicle system for brain cancer drug delivery aims to solve the issue of imprecise and invasive treatment of glioblastoma.

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