Effect of Metalation on Porphyrin-Based Bifunctional Agents in Tumor Imaging and Photodynamic Therapy

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• 作者：Nayan J. Patel ; Yihui Chen ; Penny Joshi ; Paula Pera ; Heinz Baumann ; Joseph R. Missert ; Kei Ohkubo ; Shunichi Fukuzumi ; Roger R. Nani ; Martin J. Schnermann ; Ping Chen ; Jialiang Zhu ; Karl M. Kadish ; Ravindra K. Pandey
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：March 16, 2016
• 年：2016
• 卷：27
• 期：3
• 页码：667-680
• 全文大小：734K
• ISSN：1520-4812

文摘

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.