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Polymersomes with splenic avidity target red pulp myeloid cells for cancer immunotherapy.

Nature nanotechnology

Authors: Annelies C Wauters, Jari F Scheerstra, Mandy M T van Leent, Abraham J P Teunissen, Bram Priem, Thijs J Beldman, Nils Rother, Raphaël Duivenvoorden, Geoffrey Prévot, Jazz Munitz, Yohana C Toner, Jeroen Deckers, Yuri van Elsas, Patricia Mora-Raimundo, Gal Chen, Sheqouia A Nauta, Anna Vera D Verschuur, Arjan W Griffioen, David P Schrijver, Tom Anbergen, Yudong Li, Hanglong Wu, Alexander F Mason, Marleen H M E van Stevendaal, Ewelina Kluza, Richard A J Post, Leo A B Joosten, Mihai G Netea, Claudia Calcagno, Zahi A Fayad, Roy van der Meel, Avi Schroeder, Loai K E A Abdelmohsen, Willem J M Mulder, Jan C M van Hest

Regulating innate immunity is an emerging approach to improve cancer immunotherapy. Such regulation requires engaging myeloid cells by delivering immunomodulatory compounds to hematopoietic organs, including the spleen. Here we present a polymersome-based nanocarrier with splenic avidity and propensity for red pulp myeloid cell uptake. We characterized the in vivo behaviour of four chemically identical yet topologically different polymersomes by in vivo positron emission tomography imaging and innovative flow and mass cytometry techniques. Upon intravenous administration, relatively large and spherical polymersomes accumulated rapidly in the spleen and efficiently targeted myeloid cells in the splenic red pulp. When loaded with β-glucan, intravenously administered polymersomes significantly reduced tumour growth in a mouse melanoma model. We initiated our nanotherapeutic's clinical translation with a biodistribution study in non-human primates, which revealed that the platform's splenic avidity is preserved across species.

© 2024. The Author(s).

PMID: 39085390

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