TY - GEN
T1 - Novel optical contrast agents containing both DFO and multi-RGD peptides
AU - Ye, Yunpeng
AU - Bloch, Sharon
AU - Achilefu, Samuel
PY - 2008
Y1 - 2008
N2 - A series of novel near-infrared fluorescent compounds containing both desferoxamine (DFO) and multi-RGD peptides, i.e. DFO-Cypate-(RGD) n-NH2 (1), were designed and synthesized based on a dicarboxylic acid-containing near-infrared fluorescent carbocyanine (Cypate) scaffold. The trimeric 1 (n=3) showed the strongest cellular internalization into A549 cells in vitro among the four analogs of 1 (n=1, 2, 3, 4), suggesting that such a linear array of three RGD peptide motifs might be optimal for synergistic effects on cellular internalization. The four analogs showed higher internalization than an integrin αvβ3-targeting cyclic RGD peptide analog DFO-cypate-[RGDfK(∼)] (2) after 1h of incubation, indicating that the linear arrays of multi-RGD peptides might be different from the cyclic RGD peptide analog in the internalization kinetics and mechanism of receptor targeting. Confocal microscopy showed that 1 (n=4) could localize at least in part to the mitochondria. Noteworthy, the two compounds 1 (n=2, 3) resulted in a 1.5 to 2 fold increase in fluorescence of the calcium indicator fluo4 after 30 min of incubation. These results suggest the possible effects of these compounds on the cellular function by internalization. Such a type of near-infrared fluorescent cypate analogs containing both DFO and multi-RGD peptides could provide a platform for discovering and developing novel multifunctional optical contrast agents for integrin receptor targeting as well as related tumor imaging and therapy.
AB - A series of novel near-infrared fluorescent compounds containing both desferoxamine (DFO) and multi-RGD peptides, i.e. DFO-Cypate-(RGD) n-NH2 (1), were designed and synthesized based on a dicarboxylic acid-containing near-infrared fluorescent carbocyanine (Cypate) scaffold. The trimeric 1 (n=3) showed the strongest cellular internalization into A549 cells in vitro among the four analogs of 1 (n=1, 2, 3, 4), suggesting that such a linear array of three RGD peptide motifs might be optimal for synergistic effects on cellular internalization. The four analogs showed higher internalization than an integrin αvβ3-targeting cyclic RGD peptide analog DFO-cypate-[RGDfK(∼)] (2) after 1h of incubation, indicating that the linear arrays of multi-RGD peptides might be different from the cyclic RGD peptide analog in the internalization kinetics and mechanism of receptor targeting. Confocal microscopy showed that 1 (n=4) could localize at least in part to the mitochondria. Noteworthy, the two compounds 1 (n=2, 3) resulted in a 1.5 to 2 fold increase in fluorescence of the calcium indicator fluo4 after 30 min of incubation. These results suggest the possible effects of these compounds on the cellular function by internalization. Such a type of near-infrared fluorescent cypate analogs containing both DFO and multi-RGD peptides could provide a platform for discovering and developing novel multifunctional optical contrast agents for integrin receptor targeting as well as related tumor imaging and therapy.
KW - Cellular internalization
KW - Cypate
KW - Desferrioxamine (DFO)
KW - Integrin receptor
KW - Metal binding
KW - Multimeric RGD peptide
KW - Near-infrared fluorescent probe
KW - Optical imaging
UR - http://www.scopus.com/inward/record.url?scp=43249088581&partnerID=8YFLogxK
U2 - 10.1117/12.756808
DO - 10.1117/12.756808
M3 - Conference contribution
AN - SCOPUS:43249088581
SN - 9780819470010
T3 - Progress in Biomedical Optics and Imaging - Proceedings of SPIE
BT - Optics in Health Care and Biomedical Optics III
T2 - Optics in Health Care and Biomedical Optics III
Y2 - 12 November 2007 through 15 November 2007
ER -