Author(s): Charlee Cannon, Torrance Johnson, Caleb Weaver
Mentor(s): Jessica Pullan
Institution SUU
Extracellular vesicles (EVs) are biological nanoparticles, derived from fluids like blood, saliva, urine, and milk, that have shown promise as drug delivery systems due to their innate ability to tissue localize, their selective release kinetics, and their ability to cross the blood-brain barrier (BBB). This project aims to encapsulate a glioblastoma chemotherapeutic into isolated EVs. The chemotherapeutic this project seeks to encapsulate is temozolomide (TMZ). TMZ is an imidazotetrazine derivative of the alkylating agent dacarbazine. It can spontaneously convert into its active form, MTIC (methyl-triazeno-imidazole-carboxamide), which methylates DNA at the O6 position of guanine causing cell cycle arrest and apoptosis, making TMZ effective as a chemotherapeutic treatment. Encapsulation of TMZ into EVs includes either passive or active encapsulation due to regions of partial hydrophobicity in its structure. Passive encapsulation capitalizes on hydrophobic forces by integrating the hydrophobic portions of TMZ into the hydrophobic membrane of EVs. Passive encapsulation is expected to give lower encapsulation efficiencies, a parameter used to indicate the quantity of drug successfully encapsulated, due to the partial hydrophilic nature of TMZ. Active encapsulation involves an external force, electroporation, to promote the encapsulation of TMZ into the EVs, which is more suited for more hydrophilic compounds. Due to the structural differences in TMZ and literature values for synthetic nanoparticles, active encapsulation is expected to produce greater encapsulation efficiencies for the uptake of TMZ by EVs. This project is exploring both techniques to compare the efficiencies of them to one another and aid in determining optimal TMZ concentrations.