Abstract
Bacterial inclusion bodies (IBs) are protein-based nanoparticles of a few hundred nanometers formed during recombinant protein production processes in different bacterial hosts. IBs contain active protein in a mechanically stable nanostructured format that has been broadly characterized, showing promising potential in different fields such as tissue engineering, protein replacement therapies, cancer, and biotechnology. For immunomodulatory purposes, however, the interference of the format immunogenic properties—intrinsic to IBs—with the specific effects of the therapeutic protein is still an uncovered gap. For that, active and inactive forms of the catalytic domain of a matrix metalloproteinase-9 (MMP-9 and mutMMP-9, respectively) have been produced as IBs and compared with the soluble form for dermal inflammatory effects in mmp9 knock-out mice. After protein injections in air-pouches in the mouse model, MMP-9 IBs induce local neutrophil recruitment and increase pro-inflammatory chemokine levels, lasting for at least two days, whereas the effects triggered by the soluble MMP-9 format fade out after 3 h. Interestingly, the IB intrinsic effects (mutMMP-9 IBs) do not last more than 24 h. Therefore, it may be concluded that IBs could be used for the delivery of therapeutic proteins, such as immunomodulating proteins while preserving their stability in the specific tissue and without triggering important unspecific inflammatory responses due to the protein format.
Highlights
Recombinant proteins are used for a plethora of therapeutic applications, including cancer therapy, treatment of metabolic disorders, hormone substitution, infectious diseases, thrombolysis, and reproductive disorders, among others [1,2,3,4,5]
The insoluble fraction is known as inclusion bodies (IBs), which are biophysically described as protein nanomaterials with sizes ranging from 50 to 800 nm, and are formed during recombinant protein production [6,7,8]
This study demonstrates that the IB format has only a limited inflammatory effect without interference with the specific activity of the model molecule embedded in the protein nanomaterial
Summary
Recombinant proteins are used for a plethora of therapeutic applications, including cancer therapy, treatment of metabolic disorders, hormone substitution, infectious diseases, thrombolysis, and reproductive disorders, among others [1,2,3,4,5]. The nature of IBs, which combines biological activity and rough surfaces [12,15], allows one to successfully apply these as functional nanoparticles for tissue engineering purposes [16,17]. Another explored application is the injection of targeted-IBs for cancer therapy, proving that these nanoparticles are a stable source of releasing functional proteins [5,18,19]. The exploration of protein-based nanoparticles as a new promising therapeutic format has still some uncovered gaps
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