Construction of pH-responsive dual-drug nanomedicine: Delivery of Bortezomib-Baicalein complex via bovine serum albumin nanoparticles

Abstract

Due to the versatility and diversity, dual-drug delivery systems have become a research highlight. The boronate esters hold potential for application in developing pH-responsive nanomedicine for cancer treatment. The interaction of bortezomib (BTZ) with baicalein (BAI) to form the boronate ester BTZ-BAI was confirmed via ¹H and ¹¹B NMR spectra. Additionally, bovine serum albumin (BSA) was proved as the suitable delivery agent for BTZ-BAI. The CCK-8 test suggested that the (BTZ-BAI)-BSA complex exhibited anti-glioma effects on U251 glioma cells. Cell scratch experiments showed that (BTZ-BAI)-BSA complex also reduced the healing ability of U251 glioma cells. Fluorescent imaging experiments proved that BSA NPs could be absorbed by U251 glioma cells efficiently. These findings motivated further mechanistic investigations. The BTZ-BAI exhibited a high binding affinity to BSA at 25 °C (K_a as 2.18 × 10⁵ L/mol). Molecular docking studies indicate that the stabilization of the (BTZ-BAI)-BSA complex is attributed to both hydrophobic forces and hydrogen bonds. These findings demonstrate that BAI does not only act as a synergistic anti-tumor agent, but also as a linker in the interaction of BTZ with BSA, which encouraged us to develop the procedure for the construction of the pH-responsive dual-drug nanomedicine (BTZ-BAI@BSA NPs).