Targeting Delivery of Chemotherapeutic Agents to Mammary Tumors
Abstract
Breast cancer is the second leading cause of cancer incidence and the leading cause of cancer mortality in women. Current chemotherapeutic treatments often have adverse effects primarily caused by the inefficient delivery and/or poor specificity of the compounds to breast tissues. Overall, we were interested in determining whether current therapeutic agents be redesigned to carry "tissue specific markers" to enhance their delivery and uptake in targeted tumor cells. Recently, researchers identified germlike mutations in the tumor suppressor gene BRCA1 that predisposes women to early onset breast cancer. To recapitulate this condition, our laboratory generated a Brca1 mouse model that selectively develops mammary tumors between 6-9 months of age. Using this Brca1 breast cancer model and cell lines derived from mammary tumors, phage display was used to isolate and identify peptide motifs that selectively bind to cultured Brca1 mammary tumor cell lines and were conjugated to a tracer. In vitro and in vivo efficiency and specificity of our candidate peptides toward mammary tumor cell lines and tissues was tested. The peptides were conjugated with TAT, which increased efficacy while decreasing specificity. Lastly, we identified the cellular localization of our candidate peptides.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADA405236
Entities
People
- Steven G. Brodie
Organizations
- National Institutes of Health