A modular approach toward producing nanotherapeutics targeting the innate immune system

Mandy M.T. van Leent, Anu E. Meerwaldt, Alexandre Berchouchi, Yohana C. Toner, Marianne Burnett, Emma D. Klein, Anna Vera Verschuur, Sheqouia A. Nauta, Jazz Munitz, Geoffrey Prévot, Esther M. van Leeuwen, Farideh Ordikhani, Vera P. Mourits, Claudia Calcagno, Philip M. Robson, George Soultanidis, Thomas Reiner, Rick Joosten, Heiner Friedrich, Joren C. MadsenEwelina Kluza, Roy van der Meel, Leo A.B. Joosten, Mihai G. Netea, Jordi Ochando, Zahi A. Fayad, C. Pérez-Medina, Willem J.M. Mulder, Abraham J.P. Teunissen

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Immunotherapies controlling the adaptive immune system are firmly established, but regulating the innate immune system remains much less explored. The intrinsic interactions between nanoparticles and phagocytic myeloid cells make these materials especially suited for engaging the innate immune system. However, developing nanotherapeutics is an elaborate process. Here, we demonstrate a modular approach that facilitates efficiently incorporating a broad variety of drugs in a nanobiologic platform. Using a microfluidic formulation strategy, we produced apolipoprotein A1–based nanobiologics with favorable innate immune system–engaging properties as evaluated by in vivo screening. Subsequently, rapamycin and three small-molecule inhibitors were derivatized with lipophilic promoieties, ensuring their seamless incorporation and efficient retention in nanobiologics. A short regimen of intravenously administered rapamycin-loaded nanobiologics (mTORi-NBs) significantly prolonged allograft survival in a heart transplantation mouse model. Last, we studied mTORi-NB biodistribution in nonhuman primates by PET/MR imaging and evaluated its safety, paving the way for clinical translation.
Original languageEnglish
Article numbereabe7853
Number of pages13
JournalScience Advances
Volume7
Issue number10
DOIs
Publication statusPublished - 5 Mar 2021

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