A modular approach toward producing nanotherapeutics targeting the innate immune system

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 syste...

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Bibliographic Details
Published in:	Science advances 2021-03, Vol.7 (10)
Main Authors:	van Leent, Mandy M T, Meerwaldt, Anu E, Berchouchi, Alexandre, Toner, Yohana C, Burnett, Marianne E, Klein, Emma D, Verschuur, Anna Vera D, Nauta, Sheqouia A, Munitz, Jazz, Prévot, Geoffrey, van Leeuwen, Esther M, Ordikhani, Farideh, Mourits, Vera P, Calcagno, Claudia, Robson, Philip M, Soultanidis, George, Reiner, Thomas, Joosten, Rick R M, Friedrich, Heiner, Madsen, Joren C, Kluza, Ewelina, van der Meel, Roy, Joosten, Leo A B, Netea, Mihai G, Ochando, Jordi, Fayad, Zahi A, Pérez-Medina, Carlos, Mulder, Willem J M, Teunissen, Abraham J P
Format:	Article
Language:	eng
Subjects:	Animals Health and Medicine Immune System Immunology Immunotherapy Mice Nanoparticles SciAdv r-articles Sirolimus - pharmacology Tissue Distribution
Online Access:	Get full text
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Summary:	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.
ISSN:	2375-2548 2375-2548