Breast Cancer-Targeted Nuclear Drug Delivery Overcoming Drug Resistance for Breast Cancer Chemotherapy.

摘要

Cell membrane-associated and intracellular drug resistance mechanisms are the major cause of breast cancer treatment failure. The aim of this proposal is to develop nuclear localizing nanoparticles to delivery DNA- toxins breast cancer cell nuclei to effectively overcoming the drug resistance. We finished the task 1 - To synthesize and optimize folic-acid- or LHRHfunctionalized charge reversal nanoparticles. The cationic polymer PEI and its block copolymer with degradable PCL were synthesized. The cationic PEI block amines were converted to acid labile amides to obtain the PCL-PEI/amide block copolymer. This polymer was used to fabricate the nanoparticles. The ideal nanoparticles with optimal sizes and acid-triggered negative-to-positive charge reversal properties were fabricated and characterized carefully. These nanoparticles will be characterized in vitro and in vivo.