Specific targeting of ovarian tumor-associated macrophages by large, anionic nanoparticles
Tom Haber, Yvonne R. Cornejo, Soraya Aramburo, Linda Flores, Pengpeng Cao, Alice Liu, Rachael Mooney, Megan Gilchrist, Revathiswari Tirughana, Ugochi Nwokafor, Wafa Abidi, Ernest Han, Thanh H. Dellinger, Mark T. Wakabayashi, Karen S. Aboody, Jacob M. Berlin
Abstract
-glycolic acid), and polystyrene nanoparticles administered i.p. were all found to selectively accumulate in TAMs. Quantifying silica particle uptake indicated that >80% of the injected dose was in TAMs. Particles that were smaller than 100 nm or cationic or administered intravenously (i.v.) showed no TAM targeting. Moreover, this phenomenon is likely to occur in humans because when freshly excised human surgical samples were treated with the fluorescent silica nanoparticles no interaction with healthy tissue was seen but selective uptake by TAMs was seen in 13 different patient samples. Ovarian cancer is a deadly disease that afflicts ∼22,000 women per year in the United States, and the presence of immunosuppressive TAMs at tumors is correlated with decreased survival. The ability to selectively target TAMs opens the door to targeted immunotherapy for ovarian cancer.