近日，德国不来梅雅各布大学Werner M. Nau带领的国际合作团队开发了一种可作为广谱膜载体的硼团簇。该研究于2022年3月23日发表于国际一流学术期刊《自然》杂志上。
在该文中，研究团队展示了球状的十二硼团簇，尤其是B12Br122-，可作为阴离子无机膜载体，来传递广泛的亲水性货运分子（分子量146 - 4500 Da）。该课题组发现，阳离子和中性多肽、氨基酸、神经递质、维生素、抗生素和药物可以藉由该载体携带通过脂质体膜。输运机理研究表明，载体活性与这些阴离子团簇的超高离液序列度有关。
课题组人员展示了B12Br122-是如何影响不同生物活性小分子的胞质摄取，包括抗肿瘤药物单甲基auristatin F、蛋白水解靶向的嵌合dBET1和phalloidin毒素，它们被成功递送到活细胞中用于细胞骨架标记。研究人员期待他们的超高离液序列度载体的广泛和独特的递送谱，可以成为细胞生物学、神经生物学、生理学和药学新概念研究的起点。
据悉，亲水性物质的跨膜转运对其作为治疗性化合物和标记探针的应用构成了挑战。为了解决这个问题，带电的两亲性分子被认为是经典的载体。然而，这种两亲性载体可能会发生聚集和并导致非特异性膜溶解。
附：英文原文
Title: Boron clusters as broadband membrane carriers
Author: Barba-Bon, Andrea, Salluce, Giulia, Lostal-Seijo, Irene, Assaf, Khaleel. I., Hennig, Andreas, Montenegro, Javier, Nau, Werner M.
Issue&Volume: 2022-03-23
Abstract: The membrane translocation of hydrophilic substances constitutes a challenge for their application as therapeutic compounds and labelling probes1,2,3,4. 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 146–4,500Da). 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 anions8,9,10,11,12. 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.
DOI: 10.1038/s41586-022-04413-w
Source: https://www.nature.com/articles/s41586-022-04413-w