Cyclic RGD-Functionalized closo-Dodecaborate Albumin Conjugates as Integrin Targeting Boron Carriers for Neutron Capture Therapy

Abstract

Cyclic RGD (cRGD) peptide-conjugated boronated albumin was developed to direct toward integrin αvβ3, which overexpresses on many cancer cells. A stepwise conjugation of c­[RGDfK­(Mal)] and maleimide-conjugated closo-dodecaborate (MID) to bovine serum albumin (BSA) afforded cRGD-MID-BSA, which was noncytotoxic toward both U87MG and A549 cells. As compared with l-BPA, selective antitumor activity of cRGD-MID-BSA toward U87MG cells overexpressing integrin αvβ3 was identified after thermal neutron irradiation. In vivo fluorescence live imaging of Cy5-conjugated cRGD-MID-BSA and MID-BSA revealed that both cRGD-MID-BSA and MID-BSA similarly reached the maximum accumulation during 8–12 h after injection. The selective accumulation and retention of Cy5-cRGD-MID-BSA was more pronounced than Cy5-MID-BSA after 24 h. An in vivo boron neutron capture therapy (BNCT) study revealed that the cRGD peptide ligand combination enhanced accumulation of MID-BSA into tumor cells in U87MG xenograft models. The significant tumor growth suppression was observed in U87MG xenograft models at a dose of 7.5 mg [10B]/kg after neutron irradiation.

Synthesis and cytotoxicity of the boron carrier pentagamaboronon-0-ol for boron neutron capture therapy against breast cancer

“…[ 5 7 14 ] Our compound also interacted with an essential nuclear factor kappa B related protein, IKK,[ 15 ] with an analogous docking score to its native ligand. Recent studies have explored various FR[ 16 ] and integrin αvβ3-targeted cancer therapies[ 17 ] including BNCT. The results of molecular docking analysis highlighted the potency of PGB-0-ol as a boron carrier because of the interaction between PGB-0-ol and these proteins that might enhance its cellular uptake through receptor-mediated endocytosis.…”

Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

“…To date, numerous boron-containing analogues including amino acids, 6 biochemical precursors of nucleic acids, 7 carbohydrates, 8 amines, 9 porphyrins, 10 peptides, 11 liposomes, 12 and monoclonal antibodies have been developed. 13 However, most of them do not satisfy the above criteria for clinical applications.…”

Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift

“…Due to continuous blood circulation and low immunological effect, human serum albumin (HSA) is successfully used as a core to improve the potential of therapeutic agents in theranostic constructions [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The efficiency of HSA as a carrier of cytostatics has been proven [ 16 , 17 , 18 ]. However, there is a problem not only in the selective accumulation of boron in a tumor for BNCT therapy [ 19 ], but also in the quantitative estimation of its accumulation.…”