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Acta Biomater. 2016 Jan;30:49-61. doi: 10.1016/j.actbio.2015.11.029. Epub 2015 Nov 18.

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

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA. Electronic address: jill.steinbach@louisville.edu.
2
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

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 2h, 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 24h. 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.

KEYWORDS:

Cell penetrating peptides; Drug delivery; Gene delivery; Nanoparticle

PMID:
26602822
PMCID:
PMC4695306
DOI:
10.1016/j.actbio.2015.11.029
[Indexed for MEDLINE]
Free PMC Article

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