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 - Funding Information:
The Financial support from the NIH (PO1 CA55791, RKP & HB), an RPCI support grant (P30 CA16056) and the Robert A. Welch Foundation (K.M.K., Grant E-680) is appreciated. Nayan Patel is thankful to the Department of Molecular Pharmacology and Cancer Therapeutics for providing fellowship from the NIH funded graduate student research training grant. This work was also supported by Grants-in-Aid (nos. 26620154 and 26288037 to K.O.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT); ALCA and SENTAN projects from JST, Japan (to S.F.). We thank Mary Jo Bowman for STAT3 analyses.
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 -
