Synthesis and in vitro characterization of a tissue-selective fullerene:: Vectoring C60(OH)16AMBP to mineralized bone

A tissue-vectored bisphosphonate fullerene, C-60(OH)(16)AMBP [4,4-bisphosphono-2-(polyhydroxyl-1,2-dihydro-1,2-methanofullerene[60]-61-carboxamido)butyric acid], designed to target bone tissue has been synthesized and evaluated in vitro. An amide bisphosphonate addend, in conjunction with multiple hydroxyl groups, confers a strong affinity for the calcium phosphate mineral hydroxyapatite of bone. Constant composition crystal growth studies indicate that C60(OH)(16)AMBP reduces hydroxyapatite mineralization by 50% at a concentration of 1 muM, following a non-Langmuirian mechanism. Parallel studies with C-60(OH)(30) also indicate an affinity for hydroxyapatite, but at a reduced level (28% crystal growth rate reduction at 1 muM) compared with C-60(OH)(16)AM BP. This study is the first to demonstrate that a fullerene-based material can be successfully targeted to a selected tissue as a step toward the development of such materials for medical purposes, in general. (C) 2002 Elsevier Science Ltd. All rights reserved.