TY - JOUR
T1 - In Vivo Retargeting of Poly(beta aminoester) (OM-PBAE) Nanoparticles is Influenced by Protein Corona
AU - Fornaguera, Cristina
AU - Guerra-Rebollo, Marta
AU - Lázaro, Miguel Ángel
AU - Cascante, Anna
AU - Rubio, Núria
AU - Blanco, Jerónimo
AU - Borrós, Salvador
N1 - Funding Information:
Financial support from Ministerio de Economía, Industria y Competitividad, Gobierno de España (grants RTC-2015-3751-1, SAF2015-64927-C2-1-R, SAF2015-64927-C2-2-R, Torres Quevedo 2015, and RTI2018-094734-B-C22) is acknowledged. C.F. is grateful to MINECO for their Postdoctoral Fellowship (grant Torres Quevedo 2015). The support of Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) from Generalitat de Catalunya through SGR 2017 1559 grant is also acknowledged. The authors acknowledge the kind support of Marco A. Fernández and Gerard Requena for the flow cytometry measures and analysis; Ramon Bartolí for the liver digestion experimental setup; and Júlia Meler, Irene Porcar, and Elena García-Ollé for their kind support in some experiment performance.
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/10/1
Y1 - 2019/10/1
N2 - One of the main bottlenecks in the translation of nanomedicines from research to clinics is the difficulty in designing nanoparticles actively vectorized to the target tissue, a key parameter to ensure efficacy and safety. In this group, a library of poly(beta aminoester) polymers is developed, and it is demonstrated that adding specific combinations of terminal oligopeptides (OM-PBAE), in vitro transfection is cell selective. The current study aims to actively direct the nanoparticles to the liver by the addition of a targeting molecule. To achieve this objective, retinol, successfully attached to OM-PBAE, is selected as hepatic targeting moiety. It is demonstrated that organ biodistribution is tailored, achieving the desired liver accumulation. Regarding cell type transfection, antigen presenting cells in the liver are those showing the highest transfection. Thanks to proteomics studies, organ but not cellular biodistribution can be explained by the formation of differential protein coronas. Therefore, organ biodistribution is governed by differential protein corona formed when retinol is present, while cellular biodistribution is controlled by the end oligopeptides type. In summary, this work is a proof of concept that demonstrates the versatility of these OM-PBAE nanoparticles, in terms of the modification of the biodistribution of OM-PBAE nanoparticles adding active targeting moieties.
AB - One of the main bottlenecks in the translation of nanomedicines from research to clinics is the difficulty in designing nanoparticles actively vectorized to the target tissue, a key parameter to ensure efficacy and safety. In this group, a library of poly(beta aminoester) polymers is developed, and it is demonstrated that adding specific combinations of terminal oligopeptides (OM-PBAE), in vitro transfection is cell selective. The current study aims to actively direct the nanoparticles to the liver by the addition of a targeting molecule. To achieve this objective, retinol, successfully attached to OM-PBAE, is selected as hepatic targeting moiety. It is demonstrated that organ biodistribution is tailored, achieving the desired liver accumulation. Regarding cell type transfection, antigen presenting cells in the liver are those showing the highest transfection. Thanks to proteomics studies, organ but not cellular biodistribution can be explained by the formation of differential protein coronas. Therefore, organ biodistribution is governed by differential protein corona formed when retinol is present, while cellular biodistribution is controlled by the end oligopeptides type. In summary, this work is a proof of concept that demonstrates the versatility of these OM-PBAE nanoparticles, in terms of the modification of the biodistribution of OM-PBAE nanoparticles adding active targeting moieties.
KW - OM-PBAE nanoparticles
KW - liver retargeting
KW - protein corona
KW - retinol
UR - http://www.scopus.com/inward/record.url?scp=85071625626&partnerID=8YFLogxK
U2 - 10.1002/adhm.201900849
DO - 10.1002/adhm.201900849
M3 - Article
C2 - 31478348
AN - SCOPUS:85071625626
SN - 2192-2640
VL - 8
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 19
M1 - 1900849
ER -