Synthesis and in vitro characterization of a tissue-selective fullerene: vectoring C(60)(OH)(16)AMBP 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 C(60)(OH)(16)AMBP reduces hydroxyapatite mineralization by 50% at a concentration of 1 microM, 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 microM) compared with C(60)(OH)(16)AMBP. 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.
Gonzalez
Kelly A
KA
Department of Chemistry and the Center for Nanoscale Science and Technology and the Laboratory for Biochemical and Genetic Engineering, MS-60, Rice University, PO Box 1892, Houston, TX 77251-1892, USA.
Wilson
Lon J
LJ
Wu
Wenju
W
Nancollas
George H
GH
D001842:Bone and Bones / Q000737:chemistry*; D003460:Crystallization; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite / Q000737:chemistry; D037741:Fullerenes / Q000737:chemistry / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009928:Organ Specificity; D013997:Time Factors
C470920:4,4-bisphosphono-2-(polyhydroxyl-1,2-dihydro-1,2-methanofullerene(6)-61-carboxamido)butyric acid; D004164:Diphosphonates; D037741:Fullerenes; D017886:Durapatite