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

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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)667-680
Number of pages14
JournalBioconjugate Chemistry
Volume27
Issue number3
DOIs
StatePublished - 16 Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

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