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Published on: June 12, 2021
Triggered Release Enhances the Cytotoxicity of Stable Colloidal Drug Aggregates
Eric N Donders1,2, Ahil N Ganesh1,2, Hayarpi Torosyan3
1Department of Chemical Engineering & Applied Chemistry , University of Toronto , 200 College Street , Toronto , Ontario M5S 3E5 , Canada.
Abstract:
Chemotherapeutics that self-assemble into colloids have limited efficacy above their critical aggregation concentration due to their inability to penetrate intact plasma membranes. Even when colloid uptake is promoted, issues with colloid escape from the endolysosomal pathway persist. By stabilizing acid-responsive lapatinib colloids through coaggregation with fulvestrant, and inclusion of transferrin, we demonstrate colloid internalization by cancer cells, where subsequent lapatinib ionization leads to endosomal leakage and increased cytotoxicity. These results demonstrate a strategy for triggered drug release from stable colloidal aggregates.
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