Nanoparticle-Encapsulated Doxorubicin Demonstrates Superior Tumor Cell Kill in Triple Negative Breast Cancer Subtypes Intrinsically Resistant to Doxorubicin

• Published in: Precision nanomedicine 2018-10, Vol.1 (3), p.173-182
• Main Authors: Friedman, Adam, Ye, Kenny, Rodriguez-Gabin, Alicia, Noshancuk, Joshua, Friedman, Joel, Alfieri, Alan, Navanti, Mahantesh, Landriscina, Angelo, Rosen, Jamie, Schairer, David, Makdisi, Joy, Adler, Brandon, Krausz, Aimee, McDaid, Hayley
• Format: Article
• Language: English
• ISSN: 2639-9431; 2639-9431
• DOI: 10.33218/prnano1(3).181029.1

The effect of size and release kinetics of doxorubicin-nanoparticles on anti-tumor efficacy was evaluated in a panel of human cancer cell lines, including triple-negative breast cancer (TNBC) cells that frequently demonstrate resistance to doxorubicin. Different nano-formulations of sol-gel-based Doxorubicin containing nanoparticles were synthesized. Increased cell kill in chemorefractory triple-negative breast cancer cells was associated with the smallest size of nanoparticles and the slowest release of Dox. Modeling of dose-response parameters in Dox-sensitive versus Dox-resistant lines demonstrated increased EMax and area under the curve in Dox-resistant mesenchymal TNBC cells, implying potentially favorable activity in this molecular subtype of breast cancer. Mesenchymal TNBC cells demonstrated a high rate of fluorescent bead uptake suggestive of increased endocytosis, which may partially account for the enhanced efficacy of Dox-np in this subtype. Thus, manipulation of size and release kinetics of this nanoparticle platform is associated with enhanced dose-response metrics and tumor cell kill in therapeutically recalcitrant TNBC cell models. This platform is easily customizable and warrants further exploration. [READ ARTICLE](https://precisionnanomedicine.com/article/6494)