Delivery of Nanotethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse
Abstract
The purpose of this work is to utilize monocyte/macrophage-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 monocytes/macrophages. 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 NS and NSdsDNA. 1. DNA duplexes are released from the nanoshell surface differently depending on type of laser. 2. Hydrophobic therapeutics can be complexed to nanoshells using protein scaffolds. 3. The amount and distribution of near infrared (NIR) light able to be delivered through the skull and brain tissue have been estimated. 4. The use of CT to map skull geometry and determine bone density enables a better understanding of the attenuation/scattering of NIR.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2016
- Accession Number
- AD1032853
Entities
People
- Susan E. Clare
Organizations
- Northwestern University