Cyclic RGD-Functionalized closo-Dodecaborate Albumin Conjugates as Integrin Targeting Boron Carriers for Neutron Capture Therapy
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 no...
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Published in | Molecular pharmaceutics Vol. 17; no. 10; pp. 3740 - 3747 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Chemical Society
05.10.2020
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1543-8384 1543-8392 |
DOI: | 10.1021/acs.molpharmaceut.0c00478 |