Development of theranostics albumin auristatin conjugates for combining chemotherapy with boron neutron capture therapy

Abstract

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 fluorophore-albumin based construct. We report on the synthesis of a fluorophore-labeled 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.