Aiding Nature’s Organelles: Artificial Peroxisomes Play Their Role

Abstract

A major goal in medical research is to develop artificial organelles that can implant in cells to treat pathological conditions or to support the design of artificial cells. Several attempts have been made to encapsulate or entrap enzymes, proteins, or mimics in polymer compartments, but only few of these nanoreactors were active in cells, and none was proven to mimic a specific natural organelle. Here, we show the necessary steps for the development of an artificial organelle mimicking a natural organelle, the peroxisome. The system, based on two enzymes that work in tandem in polymer vesicles, with a membrane rendered permeable by inserted channel proteins was optimized in terms of natural peroxisome properties and function. The uptake, absence of toxicity, and in situ activity in cells exposed to oxidative stress demonstrated that the artificial peroxisomes detoxify superoxide radicals and H2O2 after endosomal escape. Our artificial peroxisome combats oxidative stress in cells, a factor in various pathologies (e.g., arthritis, Parkinson's, cancer, AIDS), and offers a versatile strategy to develop other "cell implants" for cell dysfunction.

Artificial Organelles: Reactions inside Protein–Polymer Supramolecular Assemblies

“…When a nanoreactor is uptaken and preserves its activity inside cells it can be considered as a simple artificial organelle that provides specific functionality to the cell. [31] We introduced the first artificial peroxisome by co-encapsulating superoxide dismutase and lactoperoxidase/catalase inside the cavity of polymersomes. Upon uptake by THP-1/HeLa cells, this simple peroxisome efficiently detoxified both O 2 -and H 2 O 2 .…”

“…5). [31] Despite the fact that nanoreactors and artificial organelles are in their early stage of research, they prove that nanoscience-based solutions are able to support the development of molecular factories. Once nanocompartments are engineered to perform complex functions, such as cascade reactions, energy conversion, signal transduction, minimal metabolism and synthesis of molecular compounds, they can be assembled into more elaborate systems that perform as basic molecular factories.…”

“…In addition, such external molecular functionality will serve for zipping vesicles, which is an essential step for developing complex hi- Modified with permission from ref. [31]. Copyright 2013 American Chemical Society.…”

Nucleocytoplasmic Transport: A Paradigm for Molecular Logistics in Artificial Systems

“…Further, entrapping antioxidant enzymes within a polymeric membrane that was leaky to reactive oxygen species (ROS) could effectively accelerate ROS detoxification within cells under oxidative stress. [22] As a step towards multicompartmentalization, two different nanoreactors bearing two different enzymes could be encapsulated into a larger polymersome [23] and used to control a cascade reaction across the compartmental boundaries. [24] We refer the interested reader to Table 1 Ta ble 1.…”

Interfacing Functional Systems

“…Up-taken by cells, the artificial peroxisomes successfully detoxified in situ superoxide radicals and related H 2 O 2 . [33] A more complex scenario can be envisioned when different nanoreactors are interfaced to support complex cascade reactions, able to serve as core of molecular factories 18.…”