Intracellular peptide delivery using amphiphilic lipid‐based formulations

Abstract

Peptides, highly diverse by their nature, are important biochemical and pharmaceutical tools: ligands for cellular receptors, transcription factors, immunosuppressants, vaccines, etc. As the majority of their targets are intracellular, peptides need to cross the plasma membrane and gain access to the cytoplasm. However, due to their physicochemical properties, most peptides need to be entrapped by a molecular vehicle to be able to reach the cytosol compartment. In this study, we present new biological tools to enhance intracellular peptides delivery. Based on electrostatic interactions, two complementary types of amphiphilic molecules have been designed as delivery vehicles. A diverse set of fluorescently labeled peptides have successfully been delivered. This opens the avenue for the use of peptides combined to delivery vehicles as therapeutic aids.

A pyruvate decarboxylase-mediated therapeutic strategy for mimicking yeast metabolism in cancer cells

“…Enzymes are especially vulnerable, since minor alterations in protein structure can lead to loss of activity. PULSin was selected as a delivery vehicle, since this lipid formulation has previously been shown to form a complex with proteins without affecting protein activity [37]. Moreover, while most protein delivery strategies require complex conjugation procedures, a protein-PULSin complex can be formed with a simple mixing step.…”

“…Moreover, while most protein delivery strategies require complex conjugation procedures, a protein-PULSin complex can be formed with a simple mixing step. Additionally, PULSin has been shown to permit cellular internalization and endosomal escape of proteins [37]. In this study, pyruvate decarboxylase was complexed with PULSin in order to enable intracellular delivery.…”

“…PULSin works by forming a protein-lipid complex that can enter cells through endocytosis and then escape from the lysosome into the cytosol [37]. PULSin consists of the cationic lipid dioctadecylamido-glycylspermine (DOGS) [37].…”

“…PULSin works by forming a protein-lipid complex that can enter cells through endocytosis and then escape from the lysosome into the cytosol [37]. PULSin consists of the cationic lipid dioctadecylamido-glycylspermine (DOGS) [37]. Since DOGS and other cationic lipids frequently display charge-induced toxicity [38], PULSin was assembled with the MSV delivery system to increase biocompatibility.…”

Tri-peptide cationic lipids for gene delivery

“…19–20 People found that the introduction of peptide groups into lipids can prolong their half-life in vivo and enhance targeting thereof. 21 …”