Boron clusters are polyhedral boron hydrides with unique properties, and they are becoming increasingly widely used in biology and medicine, including for boron neutron capture therapy (BNCT) of cancers and in the design of novel bioactive molecules and potential drugs. Among boron cluster types, icosahedral boranes, carboranes, and metallacarboranes are particularly interesting, and there is a need for basic studies on their interaction with biologically important molecules, such as proteins. Herein, we report studies on the interaction of selected boron clusters and their derivatives with serum albumin, the most abundant protein in mammalian blood. The interaction of boron clusters with albumin was examined by fluorescence quenching, circular dichroism, dynamic and static light scattering measurements and MALDI-TOF mass spectrometry. Our results showed that metallacarboranes have the strongest interaction with albumin among the tested clusters. The observed strength of boron cluster interactions with albumin decreases in order: metallacarboranes [M(C₂B₉H₁₁)₂]⁻> carboranes (C₂B₁₀H₁₂) >> dodecaborate anion [B₁₂H₁₂]²⁻. Metallacarboranes first specifically interact with the binding cavity of albumin and then, with increasing compound concentrations, interact non-specifically with the protein surface. These findings can be of importance and are useful in the development of new bioactive compounds that contain boron clusters.

Extracellular matrix metalloproteinases (MMPs) are a family of endopeptydases which recquire a zinc ion at their active site, for proteolityc activity. There are six members of the MMP family: matrilysins, collagenases, stromelysins, gelatinases, membrane MMPs and other MMPs. Activity of MMPs is regulated at the level of gene transcription, mRNA stability, zymogene proteolitic activation, inhibition of an active enzyme and MMP degradation. Tissue inhibitors of metalloproteinases (TIMPs) are main intracellular inhibitors of MMPs. Host cells can be stimulated by tumor cells to produce MMPs by secreted interleukins, interferons, growth factors and an extracellular matrix metalloproteinase inducer (EMMPRIN). MMPs are produced by tumor cells, fibroblasts, macrophages, mast cells, polimorphonuclear neutrophiles (PMNs) and endothelial cells (ECs). MMPs affect many stages of tumor development, facilitating its growth through promoting tumor cells proliferation, invasion and migration, new blood vessels formation and blocking tumor cells apoptosis. MMPs can promote tumor development in several ways. ECM degradation results in release of peptide growth factors. Growth factors linked with cell surface or binding proteins can also be liberated by MMPs. MMPs can indirectly regulate integrin signalling or cleave E-cadherins, facilitating cell migration. MMPs support metastasis inducing an epithelial to mesenchymal transition (EMT). MMP also support transendothelial migration. MMPs support angiogenesis by releasing pro-angiogenic factors and degrading ECM to support ECs migration. Cell surface growth factor receptors are also cleaved by MMPs, which results in inhibition of tumor development, so is release of anti-angiogenic factors from ECM.

Introduction: Icosahedral boron clusters have unique properties useful in medicinal chemistry: rigidity, chemical stability, and three-dimensional aromaticity. Furthermore, these abiotic compounds have low toxicity and are stable in the biological environment. All these features ultimately give them the ability to interact with biological molecules in a different mode than organic compounds. Areas covered: In the present article, we aim to introduce boron clusters as a class of entities suitable for modifications of biomolecules to obtain a specific biological effect. We will focus on icosahedral boron clusters, as well as metallacarboranes, and their biological activity and interaction with the biological environment. Expert opinion: Boron clusters are suitable for altering structural and functional features of biomolecules and can be used in the development of new drugs and drug delivery systems. The high affinity of boron clusters, especially metallacarboranes, to albumin creates a new possibility to use them to optimize the pharmacokinetics of biologically active peptides. Boron clusters have high potential in biological and medicinal applications. Due to their peculiar properties, they can be used to optimize parameters critical for the biological activity of therapeutic substances and their affinity toward biological targets.