(161f) The Impact of Spacer Length on the Morphology and Internalization of MUC1 Aptamer-Amphiphile Nanoparticles for Targeting and Imaging Triple Negative Breast Cancer Cells
AIChE Annual Meeting
2021
2021 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Poster Session: Engineering Fundamentals in Life Science
Monday, November 8, 2021 - 3:30pm to 5:00pm
Few targeted treatment options exist for triple negative breast cancer (TNBC), leaving only chemotherapy and radiation treatments with poor response and high off-target toxicity. To address this crucial need for targeted therapy, single-stranded DNA aptamerâamphiphiles were synthesized which selectively bind to the mucinâ1 (MUC1) glycoprotein that is overexpressed in TNBC cells. These amphiphiles have a fluorescent, hydrophobic tail (1,8ânaphthalimide or 4ânitroâ1,8ânaphthalimide) which allows for easy visualization and enables self-assembly. This tail is attached to the aptamer via an alkyl spacer (C4 or C12) whose length was shown to influence the morphology of the selfâassembled structure, and thus its ability to internalize into the TNBC cells. While both the MUC1 aptamerâC4ânapthalimide spherical micelles and the MUC1 aptamerâC12ânapthalimide long cylindrical micelles showed internalization into MDAâMBâ468, SUM159, and MDA-MB-231 TNBC cells, but not the normal MCFâ10A breast cells, the cylindrical micelles showed greatly enhanced internalization. In addition, a pharmacokinetic study in mice showed a prolonged systemic circulation time of the MUC1 aptamer cylindrical micelles. There was a 4.6âfold increase in the elimination halfâlife of the aptamer cylindrical micelles, and their clearance decreased 10âfold compared to the MUC1 aptamer spherical micelles. Given the clear advantages of the cylindrical micelles, their ability to act as a drug delivery vehicle was characterized. The MUC1 aptamer cylindrical micelles by themselves were not toxic to the cells, however, when used to deliver doxorubicin to the TNBC cells, were shown to be as cytotoxic as free doxorubicin. Thus, the MUC1 aptamerâC12ânapthalimide nanofibers represent a promising vehicle that could be used for easy visualization and targeted delivery of therapeutic loads to TNBC cells.