Development of Targeted Nanogels for the Sirna-Mediated Antiangiogenesis Treatment of Breast Cancer
Abstract
The inhibition of tumor angiogenesis has significant potential as a therapeutic modality in the treatment of breast cancer. Delivering small, interfering RNA (siRNA) to activated breast microvascular endothelial cells (MVEC) can decrease the expression of proteins required during tumor angiogenesis and lead to less toxic and more effective breast cancer treatments but is limited by the absence of efficient targeted drug delivery vehicles. Nanogels (NG) composed of cross-linked polyethylene glycol and polyethylenimine (PEG-cl-PEI) were investigated for targeted siRNA delivery to activated breast MVEC. Targeted NG inhibited activated murine breast MVEC growth and vessel-like formation in vitro with little cytotoxicity irrespective of loaded siRNA. This indicates that unmodified and targeted NG inhibit MVEC by some mechanism unrelated to siRNA or detectable cytotoxicity and that first generation NG are insufficient for siRNA delivery. Similar observations delivering nucleoside analogs in other cells were overcome with biodegradable NG. Therefore, we are now assessing the potential of using biodegradable NG as a platform for further development as a targeted siRNA delivery vehicle.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2007
- Accession Number
- ADA484225
Entities
People
- Joseph A. Vetro
- R. K. Singh
- Serguei V. Vinogradov
Organizations
- University of Nebraska Omaha