A modular approach toward producing nanotherapeutics targeting the innate immune system Journal Article


Authors: van Leent, M. M. T.; Meerwaldt, A. E.; Berchouchi, A.; Toner, Y. C.; Burnett, M. E.; Klein, E. D.; Verschuur, A. V. D.; Nauta, S. A.; Munitz, J.; Prévot, G.; van Leeuwen, E. M.; Ordikhani, F.; Mourits, V. P.; Calcagno, C.; Robson, P. M.; Soultanidis, G.; Reiner, T.; Joosten, R. R. M.; Friedrich, H.; Madsen, J. C.; Kluza, E.; van der Meel, R.; Joosten, L. A. B.; Netea, M. G.; Ochando, J.; Fayad, Z. A.; Pérez-Medina, C.; Mulder, W. J. M.; Teunissen, A. J. P.
Article Title: A modular approach toward producing nanotherapeutics targeting the innate immune system
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. Copyright © 2021 The Authors, some rights reserved;
Keywords: immune system; mammals; non-human primate; heart transplantation; clinical translation; small molecule inhibitor; adaptive immune systems; apolipoprotein a-1; innate immune systems; modular approach; adaptive systems
Journal Title: Science Advances
Volume: 7
Issue: 10
ISSN: 2375-2548
Publisher: Amer Assoc Advancement Science  
Date Published: 2021-03-05
Start Page: eabe7853
Language: English
DOI: 10.1126/sciadv.abe7853
PUBMED: 33674313
PROVIDER: scopus
PMCID: PMC7935355
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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  1. Thomas Reiner
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