Immunotherapy is emerging as one of the most effective methods for treating many cancers. However, immunotherapy can still introduce significant off target toxicity and methods are sought to enable targeted immunotherapy at tumor sites. Here, we show that relatively large (&gt;100 nm), anionic nanoparticles administered IP selectively accumulate in tumor associated macrophages (TAMs). In a mouse model of ovarian cancer, fluorescently labeled silica and polystyrene nanoparticles administered intraperitoneally were exclusively found in TAMs. Quantifying silica particle uptake indicated that &gt;70% of the injected dose was in TAMs. Particles that were smaller than 100 nm or cationic or administered IV 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 many different patient samples. Ovarian cancer is a deadly disease that afflicts approximately 22,000 women per year in the US and the presence of immunosuppressive TAMs at tumors is correlated with decreased survival. The ability to selective target TAMs opens the door to targeted immunotherapy for ovarian cancer.

Specific targeting of ovarian tumor associated macrophages by large, anionic nanoparticles

256th National Meeting (2018)

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