Boron clusters as broadband membrane carriers

Andrea Barba-Bon, Giulia Salluce, Irene Lostalé-Seijo, Khaleel. I. Assaf, Andreas Hennig, Javier Montenegro () and Werner M. Nau ()
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Andrea Barba-Bon: Jacobs University Bremen
Giulia Salluce: Universidade de Santiago de Compostela
Irene Lostalé-Seijo: Universidade de Santiago de Compostela
Khaleel. I. Assaf: Jacobs University Bremen
Andreas Hennig: Jacobs University Bremen
Javier Montenegro: Universidade de Santiago de Compostela
Werner M. Nau: Jacobs University Bremen

Nature, 2022, vol. 603, issue 7902, 637-642

Abstract: Abstract The membrane translocation of hydrophilic substances constitutes a challenge for their application as therapeutic compounds and labelling probes1–4. To remedy this, charged amphiphilic molecules have been classically used as carriers3,5. However, such amphiphilic carriers may cause aggregation and non-specific membrane lysis6,7. Here we show that globular dodecaborate clusters, and prominently B12Br122−, can function as anionic inorganic membrane carriers for a broad range of hydrophilic cargo molecules (with molecular mass of 146–4,500 Da). We show that cationic and neutral peptides, amino acids, neurotransmitters, vitamins, antibiotics and drugs can be carried across liposomal membranes. Mechanistic transport studies reveal that the carrier activity is related to the superchaotropic nature of these cluster anions8–12. We demonstrate that B12Br122− affects cytosolic uptake of different small bioactive molecules, including the antineoplastic monomethyl auristatin F, the proteolysis targeting chimera dBET1 and the phalloidin toxin, which has been successfully delivered in living cells for cytoskeleton labelling. We anticipate the broad and distinct delivery spectrum of our superchaotropic carriers to be the starting point of conceptually distinct cell-biological, neurobiological, physiological and pharmaceutical studies.

Date: 2022
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DOI: 10.1038/s41586-022-04413-w

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