# Building a Simple Platform for Tailoring Peptide Surface Chemistry to Enhance Cellular Uptake of Polymer-Coated Gold Nanoparticles

## TL;DR

The paper describes a platform to modify gold nanoparticles with peptides to improve their uptake into cells, simplifying nanoparticle manufacturing for potential clinical use.

## Contribution

A simplified platform using selective reactions to anchor peptides on gold nanoparticles for enhanced cellular uptake is introduced.

## Key findings

- CPP-modified AuNPs showed significantly higher cellular uptake (∼40% in 4 h) compared to unmodified ones (∼20% in 4 h).
- CGSWQWRR@AuNPs achieved the highest uptake (∼75% in 4 h) and were prepared using a simple one-pot protocol.
- CPP–BPEI@AuNPs and CGSWQWRR@AuNPs were noncytotoxic at concentrations up to 1.0 ppm and 10 ppm, respectively.

## Abstract

Nanotherapeutic delivery requires particulate systems
composed
of only a few components yet featuring multiple capabilities to reach
the clinic. In this study, we built a platform based on selective
reactions (solid-phase peptide synthesis, peptide coupling chemistry,
and click chemistry) to enhance cellular uptake of gold nanoparticles
(AuNPs) by anchoring cell-penetrating peptides (CPPs) at the outermost
layer of the constructs. Model amphipathic peptide (MAP), trans-acting
activator of transcription (TAT), hexarginine (R6), and
arginine monomer (Arg) were attached to the surface of AuNPs synthesized
directly by using branched polyethylenimine (BPEI) polyelectrolyte.
From a different perspective, a water-soluble CGSWQWRR sequence capable
of promoting the reduction of auric species and steric stabilization
of gold colloids was also synthesized. The structure and dynamics
of particles were characterized using imaging, scattering, and spectroscopy
techniques, and their biological performance was evaluated by assessing
cell viability and cellular uptake. The nanoconstructs were noncytotoxic
up to 1.0 ppm in the case of CPP–BPEI@AuNPs (5.2 nm metallic
core) or up to 10 ppm for CGSWQWRR@AuNPs (30 nm metallic core). Those
featuring CPPs at the surface were internalized faster and to a higher
extent (∼40% in 4 h) compared to the precursor (∼20%
in 4 h). The highest cellular uptake was found for CGSWQWRR@AuNPs
(∼75% in 4 h), which mediated the membrane-wrapping process
more effectively and was prepared by the easiest protocol (one-pot,
two-reactant, no workup reaction in aqueous media). The findings of
this study simplify nanoparticle manufacturing, thereby reducing the
gap between chemical synthesis and clinical applications.