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

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 hr, 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- relative to Avidin-NPs, after 24 hr., both formulations resulted in similar internalization levels (48 and 64-fold, respectively). 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.

Peptide-modified nanoparticles inhibit formation of <em>Porphyromonas gingivalis</em> biofilms with <em>Streptococcus gordonii</em>

“…18,21 Here, we produced spherical NPs with zeta potential values for unmodified (-25 mV) and BAR-modified NPs (-7 mV) that are consistent with other avidin-NPs studies. 19,20 Since unmodified NPs have a negative surface charge, this difference can be attributed to the successful conjugation of positively charged avidin and BAR peptide to the NPs surface. In addition to confirming successful conjugation, the more positive surface charge exhibited by avidin-NPs and BARmodified NPs may also facilitate electrostatic interactions of NPs with negatively charged moieties on the P. gingivalis cell surface.…”

“…[18][19][20] Briefly, 10 mg of avidin was dissolved in 1.2 mL of 2% (w/v) sodium deoxycholate (NaDC) in PBS and warmed to 37°C. A 1 mg/mL palmitic acid-Nhydroxysuccinimide ester (PA-NHS; Sigma-Aldrich, St Louis, MO, USA) solution was prepared in 2% (w/v) NaDC and sonicated until well-mixed.…”

“…19,20 In this study, we synthesized unmodified, avidin-modified, and BAR-modified NPs and determined the overall NPs size distribution for each sample (Figure 1). The size distribution of unhydrated modified NPs trended smaller than unmodified NPs, but the average diameters of unmodified, avidin-modified, and BARmodified NPs calculated from SEM images (134±28 nm, 107±25 nm, and 99±29 nm, respectively; Table 1) were not statistically significant (P.0.05).…”

“…C6-containing NPs were synthesized using an oil-in-water (o/w) single-emulsion technique. [19][20][21] Briefly, C6 was encapsulated in 50-200 mg PLGA carboxylterminated polymer (0.55-0.75 dL/g; LACTEL ® ; DURECT Corporation, Cupertino, CA, USA). C6 was dissolved in 200 µL dichloromethane (DCM) overnight at a concentration of 15 µg/mg PLGA.…”

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

“…Steinbach et al found that decorating PLGA NPs with CPPs strikingly enhanced the cell binding and internalization of NPs. 34 Sánchez-Navarro et al reviewed various CPPs that facilitated biotherapeutics to transport across the intestinal barrier. 35 Last but not least, endosomal escape can also improve the effectiveness of drug delivery systems by protecting drug carriers from the acidified and degradative lysosome system.…”