Cell penetrating peptide-modified poly(lactic-co-glycolic acid) nanoparticles with enhanced cell internalization. (15th January 2016)

• Record Type: Journal Article
• Authors: Steinbach, Jill M.; Seo, Young-Eun; Saltzman, W. Mark
• Is Part Of: Acta biomaterialia. Volume 30(2016)
• Page Start: 49
• Page End: 61
• Publication Date: 2016-01-15
• Subjects: Nanoparticle -- Drug delivery -- Cell penetrating peptides -- Gene delivery; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2015.11.029
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: The surface modification of nanoparticles (NPs) can enhance the intracellular delivery of drugs, proteins, and genetic agents. Here we studied the effect of different surface ligands, including cell penetrating peptides (CPPs), on the cell binding and internalization of poly(lactic-co-glycolic) (PLGA) NPs. Relative to unmodified NPs, we observed that surface-modified NPs greatly enhanced cell internalization. Using one CPP, MPG (unabbreviated notation), that achieved the highest degree of internalization at both low and high surface modification densities, we evaluated the effect of two different NP surface chemistries on cell internalization. After 2 h, avidin-MPG NPs enhanced cellular internalization by 5 to 26-fold relative to DSPE-MPG NP formulations. Yet, despite a 5-fold increase in MPG density on DSPE compared to Avidin NPs, both formulations resulted in similar internalization levels (48 and 64-fold, respectively) after 24 h. Regardless of surface modification, all NPs were internalized through an energy-dependent, clathrin-mediated process, and became dispersed throughout the cell. Overall both Avidin- and DSPE-CPP modified NPs significantly increased internalization and offer promising delivery options for applications in which internalization presents challenges to efficacious delivery.