Cellular Uptake of IgG Using Collagen-Like Cell-Penetrating Peptides

Abstract

Cell-penetrating peptides (CPPs) are attractive tools for delivering macromolecules that have poor membrane permeability, such as antibodies, into cells. However, the major drawback of conventional CPPs is their instability in bodily fluids. We previously reported a novel CPP employing a collagen-like triple-helical structure that exhibited remarkable resistance against serum proteases. Herein, we report the delivery of full-length immunoglobulin G (IgG) antibody into cells using a triple-helical CPP. The CPP was conjugated to IgG via a one-pot reaction using 2-iminothiolane as a crosslinking reagent. The triple-helical CPP was less prone to being aggregated and neutralized by serum than was octaarginine, a conventional CPP. However, most of the conjugates were found to be entrapped in endosomes.

Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential

“…This complication has been addressed by designing a rigid collagen like helix comprising arginines and delivered FITC-labeled IgG to HeLa cells. 71 Also, CPPs cause their appendage to be rapidly taken up by the cells, but this very feature also provides the stumbling block for selectivity in cellular uptake. This complication is being circumvented by developing peptides that are activated to be cell penetrating upon reaching a specific target.…”

“…For example, CPPs have been shown to exhibit poor stability in vivo. This complication has been addressed by designing a rigid collagen like helix comprising arginines and delivered FITC-labeled IgG to HeLa cells …”