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Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system

The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but...

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Autores principales: Van de Steen, Alexander, Khalife, Rana, Colant, Noelle, Mustafa Khan, Hasan, Deveikis, Matas, Charalambous, Saverio, Robinson, Clare M., Dabas, Rupali, Esteban Serna, Sofia, Catana, Diana A., Pildish, Konstantin, Kalinovskiy, Vladimir, Gustafsson, Kenth, Frank, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435816/
https://www.ncbi.nlm.nih.gov/pubmed/34541345
http://dx.doi.org/10.1016/j.synbio.2021.09.001
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author Van de Steen, Alexander
Khalife, Rana
Colant, Noelle
Mustafa Khan, Hasan
Deveikis, Matas
Charalambous, Saverio
Robinson, Clare M.
Dabas, Rupali
Esteban Serna, Sofia
Catana, Diana A.
Pildish, Konstantin
Kalinovskiy, Vladimir
Gustafsson, Kenth
Frank, Stefanie
author_facet Van de Steen, Alexander
Khalife, Rana
Colant, Noelle
Mustafa Khan, Hasan
Deveikis, Matas
Charalambous, Saverio
Robinson, Clare M.
Dabas, Rupali
Esteban Serna, Sofia
Catana, Diana A.
Pildish, Konstantin
Kalinovskiy, Vladimir
Gustafsson, Kenth
Frank, Stefanie
author_sort Van de Steen, Alexander
collection PubMed
description The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but their variant chemical composition make alterations to their size, shape, or structures inherently complex. Genetically encoded protein nanocages are highly promising DDS candidates because of their modular composition, ease of recombinant production in a range of hosts, control over assembly and loading of cargo molecules and biodegradability. One example of naturally occurring nanocompartments are encapsulins, recently discovered bacterial organelles that have been shown to be reprogrammable as nanobioreactors and vaccine candidates. Here we report the design and application of a targeted DDS platform based on the Thermotoga maritima encapsulin reprogrammed to display an antibody mimic protein called Designed Ankyrin repeat protein (DARPin) on the outer surface and to encapsulate a cytotoxic payload. The DARPin9.29 chosen in this study specifically binds to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, as demonstrated in an in vitro cell culture model. The encapsulin-based DDS is assembled in one step in vivo by co-expressing the encapsulin-DARPin9.29 fusion protein with an engineered flavin-binding protein mini-singlet oxygen generator (MiniSOG), from a single plasmid in Escherichia coli. Purified encapsulin-DARPin_miniSOG nanocompartments bind specifically to HER2 positive breast cancer cells and trigger apoptosis, indicating that the system is functional and specific. The DDS is modular and has the potential to form the basis of a multi-receptor targeted system by utilising the DARPin screening libraries, allowing use of new DARPins of known specificities, and through the proven flexibility of the encapsulin cargo loading mechanism, allowing selection of cargo proteins of choice.
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spelling pubmed-84358162021-09-17 Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system Van de Steen, Alexander Khalife, Rana Colant, Noelle Mustafa Khan, Hasan Deveikis, Matas Charalambous, Saverio Robinson, Clare M. Dabas, Rupali Esteban Serna, Sofia Catana, Diana A. Pildish, Konstantin Kalinovskiy, Vladimir Gustafsson, Kenth Frank, Stefanie Synth Syst Biotechnol Article The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but their variant chemical composition make alterations to their size, shape, or structures inherently complex. Genetically encoded protein nanocages are highly promising DDS candidates because of their modular composition, ease of recombinant production in a range of hosts, control over assembly and loading of cargo molecules and biodegradability. One example of naturally occurring nanocompartments are encapsulins, recently discovered bacterial organelles that have been shown to be reprogrammable as nanobioreactors and vaccine candidates. Here we report the design and application of a targeted DDS platform based on the Thermotoga maritima encapsulin reprogrammed to display an antibody mimic protein called Designed Ankyrin repeat protein (DARPin) on the outer surface and to encapsulate a cytotoxic payload. The DARPin9.29 chosen in this study specifically binds to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, as demonstrated in an in vitro cell culture model. The encapsulin-based DDS is assembled in one step in vivo by co-expressing the encapsulin-DARPin9.29 fusion protein with an engineered flavin-binding protein mini-singlet oxygen generator (MiniSOG), from a single plasmid in Escherichia coli. Purified encapsulin-DARPin_miniSOG nanocompartments bind specifically to HER2 positive breast cancer cells and trigger apoptosis, indicating that the system is functional and specific. The DDS is modular and has the potential to form the basis of a multi-receptor targeted system by utilising the DARPin screening libraries, allowing use of new DARPins of known specificities, and through the proven flexibility of the encapsulin cargo loading mechanism, allowing selection of cargo proteins of choice. KeAi Publishing 2021-09-09 /pmc/articles/PMC8435816/ /pubmed/34541345 http://dx.doi.org/10.1016/j.synbio.2021.09.001 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Van de Steen, Alexander
Khalife, Rana
Colant, Noelle
Mustafa Khan, Hasan
Deveikis, Matas
Charalambous, Saverio
Robinson, Clare M.
Dabas, Rupali
Esteban Serna, Sofia
Catana, Diana A.
Pildish, Konstantin
Kalinovskiy, Vladimir
Gustafsson, Kenth
Frank, Stefanie
Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
title Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
title_full Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
title_fullStr Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
title_full_unstemmed Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
title_short Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
title_sort bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435816/
https://www.ncbi.nlm.nih.gov/pubmed/34541345
http://dx.doi.org/10.1016/j.synbio.2021.09.001
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