(257e) Protein-Polymer Core-Shell Nanoparticles as Non-Viral Gene Delivery Vehicles

Authors: 
Segura, T., UCLA
Zhang, J., University of California, Los Angeles
Lei, Y., University of California, Los Angeles
Lu, Y., University of California, Los Angeles


In this talk the use of cationic protein-polymer core-shell (PPCS) nanoparticles for non-viral gene delivery is investigated. PPCS nanoparticles consists of three modules, a protein core, a cationic polymer shell, and reactive terminal end groups. Thus, there are three locations where functionality can be added. The nanoparticles are synthesized using situ atom transfer radical polymerization (ATPR), by modifying the protein core with α-Bromoisobutyryl bromide and subsequently polymerizing the monomer 2-(Dimethylamino)ethyl acrylate. Through varying the polymerization time, mono-dispersed water-soluble cationic nanoparticles with diameter ranging from 5nm to 15nm and surface potentials ranging from +8mV to +28mV were synthesized. These cationic nanoparticles were able to condense plasmid DNA resulting in DNA nanoparticles of 70nm in diameter and surface potential between 20 and 30mV. The ability of DNA/PPCS to mediate gene transfer was studied using HEK293 cells, NIH/3T3 cells and D1 cells (a mouse mesenchymal stem cell line). It was observed that transgene expression was similar to that achieved with linear PEI for HEK293 and NIH/3T3 cells but not for D1 cells, where gene transfer with linear PEI was still more efficient. Gene transfer was a function of the PPCS nanoparticle diameter and the number of nanoparticles used to form particles with DNA. Overall PPCS are efficient non-viral gene delivery vehicles, which could offer an alternative strategy to design efficient non-viral gene delivery vehicles.