Abstract: 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

Cite: Wang M. , Moskalev I.A. , Zakharova O.D. , Kasatova A.I. , Silnikov V.N. , Popova T.V. , Godovikova T.S.
Development of Theranostics Albumin Auristatin Conjugates for Combining Chemotherapy with Boron Neutron Capture Therapy
Journal of biology and today’s world. 2024. V.13. N1. P.000-007. DOI: 10.35248/2322-3308-13.1.001

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Submitted:	Jan 25, 2024
Published print:	Feb 26, 2024

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