Maleimide-functionalized closo-dodecaborate albumin conjugates (MID-AC): Unique ligation at cysteine and lysine residues enables efficient boron delivery to tumor for neutron capture therapy

J Control Release. 2016 Sep 10:237:160-7. doi: 10.1016/j.jconrel.2016.07.017. Epub 2016 Jul 12.

Abstract

Maleimide-conjugating closo-dodecaborate sodium form 5c (MID) synthesized by the nucleophilic ring-opening reaction of closo-dodecaborate-1,4-dioxane complex 2 with tetrabutylammonium (TBA) azide was found to conjugate to free SH of cysteine and lysine residues in BSA under physiological conditions, forming highly boronated BSA that showed high and selective accumulation in tumor and significant tumor growth inhibition in colon 26 tumor-bearing mice subjected to thermal neutron irradiation.

Keywords: Albumin modification; Boron delivery system; Boron neutron capture therapy (BNCT); Closo-dodecaborate; Maleimide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron / administration & dosage*
  • Boron / therapeutic use
  • Boron Compounds / chemistry*
  • Boron Neutron Capture Therapy / methods*
  • Cell Line
  • Cysteine / chemistry
  • Drug Carriers / chemistry
  • Female
  • Lysine / chemistry
  • Maleimides / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Neoplasms / radiotherapy*
  • Serum Albumin, Bovine / chemistry*

Substances

  • Boron Compounds
  • Drug Carriers
  • Maleimides
  • dodecaborate
  • Serum Albumin, Bovine
  • Lysine
  • Cysteine
  • Boron