New concepts that combine biomolecules with stable, safe and robust synthetic assemblies at the nanoscale are on focus in medicine, to provide novel solutions for therapy and diagnostics. Catalytic compartments are generated by incorporation of imembrane proteins in synthetic membranes of nanocompartments simultaneously with enzyme/proteins encapsulation inside. Such catalytic nanocompartments support a novel strategy to generate multifunctional systems, and provide optimum properties and functionality to serve as artificial organelles, with high potential for future protein therapy solutions. Here, we present catalytic compartments with triggered activity based on protein-polymer assemblies serving as distinct spaces for desired complex reactions “on demand”. In this respect, spherical nanocompartments with membranes mimicking the cell membrane properties have been self-assembled from combinations of amphiphilic copolymers and biomolecules (enzymes, membrane proteins). Chemically modified membrane proteins inserted into the polymer membrane of the nanocompartments provide a selectively control of the exchange of substrates and products with the environment upon the presence of a specific stimulus. These stimuli-responsive compartments preserve their architecture, whilst allowing specific in situ enzymatic reactions. They serve both to protect the encapsulated active compounds (enzymes, proteins, mimics) and to allow them to fulfill their bioactivity. Catalytic nanocompartments are complementary systems to drug delivery systems, with advantages to avoid uncontrolled release of the encapsulated enzyme/protein, to be nontoxic and to be functional “on demand”, in specific conditions (a change of pH, presence of a specific biomolecule, etc). Upon up-take in cells, the catalytic nanocompartments remain functional, in a similar manner as the natural cellular organelles. Upon injection into vertebrate zebrafish embryo model these artificial organelles showed in vivo tolerability, successful preservation of their architecture, and in situ regulation of the encapsulated enzymes activity. Such artificial organelles with triggered activity open new avenues in various domains, as for example protein therapy or biosensing approaches.

Biomimetic artificial organelles with in vitro and in vivo reduction triggered activity

254th National Meeting (2017)

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