In Vivo Retargeting of Poly(beta aminoester) (OM‐PBAE) Nanoparticles is Influenced by Protein Corona

Abstract

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.

Engineering precision nanoparticles for drug delivery

“…Once formed, this corona will dictate the distribution of the NP, and can compromise stability of both the NP and its cargo 61,96,98 . Recent investigations have sought to determine how the specific corona biomolecules alter NP distribution and tissue-specific targeting [99][100][101] . For example, coronas containing apolipoprotein E (ApoE) act as targeting moieties for low-density lipoprotein receptors, which leads to NP delivery to hepatocytes and, in some instances, across the blood-brain barrier (BBB) 99,[102][103][104] .…”

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

“…Then the ASO was released in HSC specifically and therefore effectively inhibits the expression of type I collagen, and thus reduces the liver fibrosis in mouse models. In addition, after modified with retinol, poly(beta-amino ester) polymers combined with terminal oligopeptides (OM-PBAE) increased the adsorption of apolipoproteins in the corona, thus enhanced active targeting to the liver, where receptors for these proteins are located (Fornaguera et al, 2019). 2-mercapto ethanol modified AuNSs can reduce the amount of adsorbed PC, and thus enhanced the active targeting ability of 2Rb17c nanobody to epidermal growth factor 2 receptor expressing tumor cells (D'Hollander et al, 2017).…”

Emerging Concepts of Nanobiotechnology in mRNA Delivery

“…Effective organ targeting is beneficial for following transfection in cells of interest that finally take up mRNA. Active targeting using targeting molecules is one strategy for specific organ uptake, such as platelet‐endothelial cell adhesion molecules‐1 (PECAM‐1) antibody modified LNPs for the enhanced delivery of mRNA to the lungs [34] and retinol‐modified oligopeptides with binding affinity to retinol‐binding protein for preferential liver accumulation [35] . Despite the high efficacy resulting from the specific interaction between the targeting moiety and the receptors, challenges including complex modification processes and instability upon exposure biological barriers which would hinder large‐scale production and clinical applications.…”