Cell-penetrating peptides with intracellular organelle targeting

Abstract

One of the major limiting steps in order to have an effective drug is the passage through one or more cell membranes to reach its site of action. To reach the action-site, the specific macromolecules are required to be delivered specifically to the cell compartment/organelle in their (pre)active form. Areas covered: In this review, we will discuss cell-penetrating peptides (CPPs) developed in the last decade to transport small RNA/DNA, plasmids, antibodies, and nanoparticles into specific sites of the cell. The article describes CPPs in complex with cargo molecules that target specific intracellular organelles and their potential for pharmacological or clinical use. Expert opinion: Organelle targeting is the ultimate goal to ensure selective delivery to the site of action in the cells. CPP technologies represent an important strategy to address drug delivery to specific intracellular compartments by covalent conjugation to targeting sequences, potentially enabling strategies to combat genomic diseases as well as infections, cancer, neurodegenerative and hereditary diseases. They have proven to be successful in delivering various therapeutic agents into cells however, further in vivo experiments and clinical trials are required to demonstrate the efficacy of this technology.

Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem

“…The predominant approach for targeting CPP-bound cargo calls for the fusion of canonical signal sequences to cargo proteins, or even to the CPP tag itself (reviewed in (54)). Using this methodology, cargos have been delivered to the nucleus (55, 56), nucleolus (57), lysosome (58), peroxisome (55), the mitochondria (55, 59, 60) and the endoplasmic reticulum (55, 61), to name a few.…”

A versatile cell-penetrating peptide-adaptor system for efficient delivery of molecular cargos to subcellular destinations

“…CPP-mediated delivery of cargo to places other than the cytoplasm has long been a goal of developing therapeutics as there are many sites of action [28]. By addition of localization signals to cargo proteins, delivery to the nucleus, peroxisomes and endoplasmic reticulum was achieved.…”

Intracellular Delivery of Native Proteins Facilitated by Cell‐Penetrating Poly(disulfide)s

“…[3] In fact, of all existing therapeutic antibodies,a lmost all of them target cell-surface antigens overexpressed in malignant cells in order to bypass the need for intracellular delivery. Although various approaches for intracellular protein delivery have thus far been reported, [5][6][7][8][9] most rely on endocytosisbased cell uptake mechanisms and necessitate significant genetic or chemical modifications to the protein. Although various approaches for intracellular protein delivery have thus far been reported, [5][6][7][8][9] most rely on endocytosisbased cell uptake mechanisms and necessitate significant genetic or chemical modifications to the protein.…”