Closo-Dodecaborate-conjugated human serum albumins: Preparation and in vivo selective boron delivery to tumor

Abstract

Maleimide-functionalized closo-dodecaborate (MID) and isothiocyanate-functionalized closo-dodecaborate (ISD) were synthesized from closo-dodecaborate via ring opening reaction of 1,4-dioxane-closo-dedecaborate complex 1 with ammonia. MID was found to possess highest conjugation efficacy to bovine serum albumin among three closo-dodecaborate derivatives, MID, ISD, and 1. The conjugation reaction of MID to human serum albumin (HSA) proceeded under PBS buffer conditions (pH 7.4). Boron distribution studies in colon 26 tumor-bearing mice revealed that HSA-MID was highly accumulated in tumor (23 ppm B), whereas boron concentrations in other organs such as liver, kidney and spleen were low (3~8 ppm B).