Drug delivery to peroxisomes: employing unique trafficking mechanisms to target protein therapeutics.

Stanley R Terlecky, Jay I Koepke

Journal: Advanced drug delivery reviews 2007;59(8):739-47

PMID: 17659806

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Abstract

Peroxisomes are multifunctional organelles of all human cells, responsible for a variety of essential biochemical and metabolic processes including alpha- and beta-oxidation of specific fatty acids, plasmalogen biosynthesis and glyoxylate detoxification. Inborn errors of biogenesis or in the ability to synthesize or properly traffic specific enzymes to peroxisomes result in devastating human disease. The organelle has also emerged as a contributor to cellular oxidative stress through its ability to generate hydrogen peroxide. Unlike most other organelles, the peroxisome's import apparatus will accommodate fully folded, oligomeric and co-factor-bound substrates. The strategies outlined here are designed to take advantage of this unique mechanism to target protein therapeutics. Emphasis is also placed on how to deliver these bioactive molecules into cells to engage the peroxisomal protein import machine. The critical antioxidant enzyme catalase has been successfully delivered and targeted by many of the approaches detailed herein; these examples will be discussed.

Address: Department of Pharmacology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, Michigan 48201 USA. [email protected]

DOI: 10.1016/j.addr.2007.06.005

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MeSH Terms: Acatalasia, Biological Transport, Active, Catalase, Drug Delivery Systems, Endosomes, Humans, Hydrogen Peroxide, Hyperoxaluria, Intracellular Space, Membrane Proteins, Microscopy, Fluorescence, Oxidation-Reduction, Oxidative Stress, Peptides, Peroxisomal Disorders, Peroxisome-Targeting Signal 1 Receptor, Peroxisomes, Protein Transport, Receptors, Cytoplasmic and Nuclear, Zellweger Syndrome