(718i) Effect of Different Oligoarginine Modification On Cellular Uptake and Intracellular Mechanism of Polymeric Nanoparticles

The biological lipophilic cell membrane can block various therapeutic macromolecules (DNA, RNA, protein etc.) to reach their targets inside the cells; thus an effective intracellular drug delivery carrier capable of facilitating drugs to overcome the cell membrane is required. With superior cellular uptake capacity and potential direct transduction mechanism, cell-penetrating peptide has gained much attention in the past years. Among cell-penetrating peptides, oligoarginine has been widely used and has successfully delivered various cargoes to reach their intracellular targets, while the number and distribution of arginines plays a key role in its uptake capacity and mechanisms. As peptide vectors, however, oligoarginine as well as other cell-penetrating peptides have disadvantages such as low drug carrying capacity and weak cargo protection. Therefore, we intend to introduce this peptide into biodegradable polymeric nanoparticles through surface modification, to increase payload, protect the cargo and prolong the release. More importantly, we also aim at studying how the length and density of oligoarginine on the polymeric particle surface can affect its cellular uptake as well as internalization mechanism.

We report here the design and synthesis of cell penetration polymeric nanoparticles. Biodegradable block copolymer poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) was synthesized and modified by three different oligoarginines (number of arginine residues = 1, 4 and 8) via one-step click chemistry. Narrowly-dispersed nanoparticles were obtained by self-assembly of modified block polymers, while particle surface was found highly positively charged after modification. Second, we evaluated the interaction of these particles with cells in vitro. They exhibited no cytotoxicity up to 100 µg/mL. Further experiments will be conducted on flow cytometry and confocal microscope to investigate the cellular uptake and internalization mechanism of oligoarginine-modified nanoparticles with different oligoarginine length and density. In short, this study can not only provide a novel carrier but also illustrate effect of different surface modification for intracellular drug delivery.