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Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

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Northwestern University Evanston United States

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The purpose of this work is to utilize monocytemacrophage-enabled delivery, a novel therapeutic delivery system that we pioneered, to increase the effectiveness and decrease the toxicity of the treatment of intracranial metastases from primary breast cancer. Our objective in this proposal is to deliver therapeutics to brain metastases using a nanoshell NS-double-stranded DNA dsDNA-drug complex loaded within monocytesmacrophages. Once present within the metastasis, we aim to release the drug by transcranial irradiation at near-infrared NIR wavelengths. Our studies have provided fundamental information on a number of aspects of the delivery of therapeutics by NSdsDNA. 1. It is of key importance that the therapeutic is soluble and stable in aqueous solution 2. Dehybridization of DNA duplexes on the nanoshell surface is a thermal phenomenon. 3. Although doxorubicin is a DNA intercalating agent, it may distort the double helix such that it is not a secure cargo. 4.We have estimated, to the best of our knowledge for the first time, the amount and distribution of near infrared light able to be delivered through the skull and brain tissue.

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Technical Report,15 Sep 2014,14 Sep 2015



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Approved For Public Release;

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