Editors' ChoiceCancer

These nanoparticles are just right

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Science Translational Medicine  12 Aug 2020:
Vol. 12, Issue 556, eabd4773
DOI: 10.1126/scitranslmed.abd4773

Abstract

Optimizing nanoparticle size, charge, and route of delivery enables highly efficient and selective targeting of tumor-associated macrophages.

Immunotherapy uses the patient’s own immune system to destroy cancerous cells, but for patients with ovarian cancer, immunotherapy has not been effective. Tumor-associated macrophages (TAMs) usually express immunosuppressive factors that protect the cancer cells from attack. To address this problem, Haber et al. developed a nanoparticle platform to target and shut down TAMs. Although small nanoparticles have long been explored as a cancer therapeutic, they have notoriously low efficiency in reaching tumors when delivered intravenously. As an alternative, the authors delivered nanoparticles directly into the peritoneal cavity in mouse models. Using this route, they found that negatively charged nanoparticles larger than 200 nm selectively accumulated in ovarian tumors. Furthermore, the targeting was found to be both selective and efficient. To quantify the efficiency of delivery, the authors made silica nanoparticles with a gold core to allow for quantification using mass spectrometry. They found that tumors harvested 4 days after injection of the gold-doped nanoparticles contained 84% of the injected dose. In addition, 94% of the tumors, both primary and metastatic, were associated with one or more nanoparticle.

Within the tumors, the nanoparticles were found overwhelmingly in the macrophages, and 87% of TAMs isolated from the murine tumors were found to be associated with a nanoparticle. A similar affinity for TAMs was seen when the experiment was repeated with ovarian tumors harvested from 13 human patients. In each case, ex vivo incubation of the tumor tissue with negatively charged 500-nm nanoparticles resulted in human TAMs taking up the particles.

The identification of nanoparticle size, charge, and delivery parameters that improve selective targeting of TAMs opens new opportunities to selectively target and shut down these immunosuppressive macrophages. It may now be possible to sensitize ovarian tumors to immunotherapy using new formulations of nanoparticles loaded with drugs to shut down TAM activity. If this approach is successful, immunotherapies that have proven effective in other cancers may provide improved efficacy and hope for patients with ovarian cancer.

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