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Wiklander OPB, Mamand DR, Mohammad DK, Zheng W, Jawad Wiklander R, Sych T, Zickler AM, Liang X, Sharma H, Lavado A, Bost J, Roudi S, Corso G, Lennaárd AJ, Abedi-Valugerdi M, Mäger I, Alici E, Sezgin E, Nordin JZ, Gupta D, Görgens A, El Andaloussi S
Nat Biomed Eng 8 (11) 1453-1468 [2024-11-00; online 2024-05-20]
Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody-drug conjugates.
PubMed 38769158
DOI 10.1038/s41551-024-01214-6
Crossref 10.1038/s41551-024-01214-6
pmc: PMC11584392
pii: 10.1038/s41551-024-01214-6