TY - JOUR
T1 - Effect of Metalation on Porphyrin-Based Bifunctional Agents in Tumor Imaging and Photodynamic Therapy
AU - Patel, Nayan J.
AU - Chen, Yihui
AU - Joshi, Penny
AU - Pera, Paula
AU - Baumann, Heinz
AU - Missert, Joseph R.
AU - Ohkubo, Kei
AU - Fukuzumi, Shunichi
AU - Nani, Roger R.
AU - Schnermann, Martin J.
AU - Chen, Ping
AU - Zhu, Jialiang
AU - Kadish, Karl M.
AU - Pandey, Ravindra K.
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/3/16
Y1 - 2016/3/16
N2 - Herein we report the syntheses and comparative photophysical, electrochemical, in vitro, and in vivo biological efficacy of 3-(1′-hexyloxy)ethyl-3-devinylpyropheophorbide-cyanine dye (HPPH-CD) and the corresponding indium (In), gallium (Ga), and palladium (Pd) conjugates. The insertion of a heavy metal in the HPPH moiety makes a significant difference in FRET (Förster resonance energy transfer) and electrochemical properties, which correlates with singlet oxygen production [a key cytotoxic agent for photodynamic therapy (PDT)] and long-term in vivo PDT efficacy. Among the metalated analogs, the In(III) HPPH-CD showed the best cancer imaging and PDT efficacy. Interestingly, in contrast to free base HPPH-CD, which requires a significantly higher therapeutic dose (2.5 μmol/kg) than imaging dose (0.3 μmol/kg), the corresponding In(III) HPPH-CD showed excellent imaging and therapeutic potential at a remarkably low dose (0.3 μmol/kg) in BALB/c mice bearing Colon26 tumors. A comparative study of metalated and corresponding nonmetalated conjugates further confirmed that STAT-3 dimerization can be used as a biomarker for determining the level of photoreaction and tumor response.
AB - Herein we report the syntheses and comparative photophysical, electrochemical, in vitro, and in vivo biological efficacy of 3-(1′-hexyloxy)ethyl-3-devinylpyropheophorbide-cyanine dye (HPPH-CD) and the corresponding indium (In), gallium (Ga), and palladium (Pd) conjugates. The insertion of a heavy metal in the HPPH moiety makes a significant difference in FRET (Förster resonance energy transfer) and electrochemical properties, which correlates with singlet oxygen production [a key cytotoxic agent for photodynamic therapy (PDT)] and long-term in vivo PDT efficacy. Among the metalated analogs, the In(III) HPPH-CD showed the best cancer imaging and PDT efficacy. Interestingly, in contrast to free base HPPH-CD, which requires a significantly higher therapeutic dose (2.5 μmol/kg) than imaging dose (0.3 μmol/kg), the corresponding In(III) HPPH-CD showed excellent imaging and therapeutic potential at a remarkably low dose (0.3 μmol/kg) in BALB/c mice bearing Colon26 tumors. A comparative study of metalated and corresponding nonmetalated conjugates further confirmed that STAT-3 dimerization can be used as a biomarker for determining the level of photoreaction and tumor response.
UR - http://www.scopus.com/inward/record.url?scp=84962230659&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.5b00656
DO - 10.1021/acs.bioconjchem.5b00656
M3 - Article
C2 - 26735143
AN - SCOPUS:84962230659
SN - 1043-1802
VL - 27
SP - 667
EP - 680
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 3
ER -
