Design of Vaterite Nanoparticles for Controlled Delivery of Active Immunotherapeutic Proteins

Levi Collin Nelemans, Ghizlane Choukrani, Natasha Ustyanovska-Avtenyuk, Valerie R. Wiersma, Lars Dähne, Edwin Bremer*

*Corresponding author voor dit werk

    Onderzoeksoutput: ArticleAcademicpeer review

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    Despite clinical advances in immunotherapy, still many therapeutics cause dose-limiting (auto)immune-mediated toxicities. Nanoparticle-based drug delivery systems (DDS) can improve cancer immunotherapy through site-specific delivery and controlled release of immunotherapeutics in the tumor microenvironment (TME). However, DDS face several challenges, including unspecific release. To address this, vaterite nanoparticles (VNPs) that selectively release immunotherapeutic proteins at low pH conditions find in the TME, are established previously. In the current study, these VNPs are further modified for active targeting without affecting the loaded protein activity, exemplified with Tumor Necrosis Factor α (TNF). Specifically, VNPs are coated with gelatin, a matrix-metalloprotease sensitive polymer which provides functional groups for further conjugation. Subsequently, streptavidin is covalently linked to the gelatin shell by amine-epoxy chemistry, enabling coupling of any biotinylated ligand. Exemplified by biotinylated cetuximab and rituximab, targeted VNPs selectively bind to cells expressing epidermal growth factor receptor (EGFR) or CD20, respectively. Importantly, TNF remains functionally active after the modification steps, as VNP treatment increased ICAM-1 expression on FaDu cells and activated NFκB signaling in a Jurkat.NFκB-luciferase cell line model. In conclusion, a targetable vaterite-based DDS is produced that allows for easy surface modification with any biotinylated ligand that may find broad applications in tumor-selective immunotherapy.

    Originele taal-2English
    Artikelnummer2300153
    Aantal pagina's11
    TijdschriftParticle and Particle Systems Characterization
    Volume41
    Nummer van het tijdschrift7
    DOI's
    StatusPublished - jul.-2024

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