Nuclear Drug Delivery for Breast Cancer Chemotherapy
Abstract
Chemo-resistant breast cancer cells overexpress not only membrane-associated but also many cytosolic drug-resistance mechanisms to limit the access of DNA-toxins to the nucleus, causing low chemotherapeutic efficacy. The project aims to synthesize and evaluate a conjugate that can enter and deliver DNA-toxins doxorubicin (DOX) or camptothecin (CPT) to the nuclei of breast cancer cells. In this project, a polyethyleneimine (PEI) was used as a nuclear localizing carrier, and was functionalized with folic acid as targeting groups and CPT as a DNA-toxin. The PEI carrier was modified to be negatively charged in the bloodstream to shield its cationic charges and thereby inhibit its interaction with cells before reaching tumors, but once in acidic tumor interstitium or tumor cells' acidic lysosomes, the PEl is regenerate for cellular uptake and nuclear localization. The PEI-based conjugate could enter the breast cancer cells efficiently and traverse to their nuclei. The carried CPT showed much higher cytotoxicity to breast cancer cells than CPT itself. Similarly, a cationic polylysine-based conjugate was also synthesized and similar results were obtained.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA501584
Entities
People
- William J. Murdoch
- Youqing Shen
Organizations
- University of Wyoming