Meiling Wang2, Ivan A. Moskalev2, Olga D. Zakharova1, Anna I. Kasatova3, Vladimir N. Silnikov1,Tatyana V. Popova1,2*, Tatyana S. Godovikova1,2*
Combining boron neutron capture therapy with chemotherapy can provide good therapy efficacy and is of great relevance today. In this study, we focused on serum albumin, a well-known drug delivery system, and developed homocysteine-functionalized boron albumin conjugate with chemotherapeutic molecules (monomethyl auristatin E, MMAE and auristatin F, MMAF). The new N-acylated homocysteine thiolactone bearing a cobalt bis (dicarbollide) derivative was used to create the fluorophorealbumin based construct. We report on the synthesis of a fluorophorelabeled boron-homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare a novel multifunctional constructs with the antitubulin agents MMAE or MMAF. We demonstrate that boron-equipped albumin conjugate with MMAE was more potent than MMAF conjugate, in the killing tumor cells. The half-maximal Inhibitory Concentration (IC50) of the designed theranostics was not less than 0.034 µM relative to T98G glioma cells with the correlation coefficient not less than R=0.88, and not less than 0.97 µM relative U 87 glioma cells with the correlation coefficient not less than R=0.71. Both theranostics are observed in vitro in the cytoplasm of human glioblastoma cells T98G as dotted small vesicles indicating an endocytic mechanism of internalization.