Abstract
Photodynamic therapy (PDT) has been extensively explored for malignant tissue treatment. In this work, we successfully synthesized and characterized a series of porphyrin compounds by connecting porphyrin units with alkyl chains, which were then coordinated with palladium to yield related metal complexes, named Pd-Monopor, Pd-Dipor, and Pd-Tripor, respectively. The generation of reactive oxygen species (ROS) of six porphyrin compounds was investigated by the dichlorofluorescein (DCFH) method. As expected, the palladium porphyrin complexes showed the higher efficiency of ROS generation relative to free base porphyrins, probably due to the heavy atom effect. Remarkably, the efficiency of ROS generation increased with the number of porphyrin units in the photosensitizers. The order of ROS generation efficiency of the synthesized porphyrins was Pd-Tripor > Tripor > Dipor > Pd-Monopor > Pd-Dipor > Monopor. MTT assay suggested the good biocompatibility of the synthesized photosensitizers in the dark. Upon light irradiation, the palladium porphyrin complex exhibited higher therapeutic activity than free base porphyrin. The half-maximal inhibitory concentration (IC50) of Tripor and Pd-Tripor under light irradiation was calculated to be 18.2 and 9.6 μM, respectively. The cellular uptake and subcellular localization experiments indicated that Tripor was mainly localized in the lysosomes of cancer cells.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
X. Xue, A. Lindstrom and Y. Li, Porphyrin-Based Nanomedicines for Cancer Treatment, Bioconjugate Chem., 2019, 30(6), 1585–1603.
M. Ethirajan, Y. Chen, P. Joshi and R. K. Pandey, The role of porphyrin chemistry in tumor imaging and photo-dynamic therapy, Chem. Soc. Rev., 2011, 40(1), 340–362.
S. Zhu, S. Yao, F. Wu, L. Jiang, K.-L. Wong, J. Zhou and K. Wang, Platinated porphyrin as a new organelle and nucleus dual-targeted photosensitizer for photodynamic therapy, Org. Biomol. Chem., 2017, 15(27), 5764–5771.
S. Zhu, F. Wu, K. Wang, Y. Zheng, Z. Li, X. Zhang and W. K. Wong, Photocytotoxicity, cellular uptake and subcellular localization of amidinophenylporphyrins as potential photodynamic therapeutic agents: An in vitro cell study, Bioorg. Med. Chem. Lett., 2015, 25(20), 4513–4517.
R. Vankayala and K. C. Hwang, Near-Infrared-Light-Activatable Nanomaterial-Mediated Phototheranostic Nanomedicines: An Emerging Paradigm for Cancer Treatment, Adv. Mater., 2018, 30(23), e1706320.
F. Wu, H. Su, Y. Cai, W.-K. Wong, W. Jiang and X. Zhu, Porphyrin-Implanted Carbon Nanodots for Photoacoustic Imaging and in Vivo Breast Cancer Ablation, ACS Appl. Bio Mater., 2018, 1(1), 110–117.
F. Wu, L. Chen, L. Yue, K. Wang, K. Cheng, J. Chen, X. Luo and T. Zhang, Small-Molecule Porphyrin-Based Organic Nanoparticles with Remarkable Photothermal Conversion Efficiency for in Vivo Photoacoustic Imaging and Photothermal Therapy, ACS Appl. Mater. Interfaces, 2019, 11(24), 21408–21416.
K. Ding, Y. Zhang, W. Si, X. Zhong, Y. Cai, J. Zou, J. Shao, Z. Yang and X. Dong, Zinc(II) Metalated Porphyrins as Photothermogenic Photosensitizers for Cancer Photodynamic/Photothermal Synergistic Therapy, ACS Appl. Mater. Interfaces, 2018, 10(1), 238–247.
Y. Zheng, S. Zhu, L. Jiang, F. Wu, C. Huang, Z. Li, K.-L. Wong, Z. Xu and K. Wang, Synthesis, singlet oxygen generation, photocytotoxicity and subcellular localization of azobisporphyrins as potentially photodynamic therapeutic agents in vitro cell study, J. Porphyrins Phthalocyanines, 2017, 21(02), 122–127.
J. Jiang, D. Liu, Y. Zhao, F. Wu, K. Yang and K. Wang, Synthesis, DNA binding mode, singlet oxygen photogeneration and DNA photocleavage activity of ruthenium compounds with porphyrin-imidazo[4,5-f]phenanthroline conjugated ligand, Appl. Organomet. Chem., 2018, 32(9), e4468.
F. Wu, J. Chen, Z. Li, H. Su, K. C.-F. Leung, H. Wang and X. Zhu, Red/Near-Infrared Emissive Metalloporphyrin-Based Nanodots for Magnetic Resonance Imaging-Guided Photodynamic Therapy In Vivo, Part. Part. Syst. Charact., 2018, 35(9), 1800208.
F. Wu, L. Yue, H. Su, K. Wang, L. Yang and X. Zhu, Carbon Dots @ Platinum Porphyrin Composite as Theranostic Nanoagent for Efficient Photodynamic Cancer Therapy, Nanoscale Res. Lett., 2018, 13(1), 357.
R. Bonnett, Photosensitizers of the porphyrin and phthalo-cyanine series for photodynamic therapy, Chem. Soc. Rev., 1995, 24(1), 19–33.
M. Kempa, P. Kozub, J. Kimball, M. Rojkiewicz, P. Kuś, Z. Gryczyński and A. Ratuszna, Physicochemical properties of potential porphyrin photosensitizers for photodynamic therapy, Spectrochim. Acta, Part A, 2015, 146, 249–254.
L. Yang, H. Li, D. Liu, H. Su, K. Wang, G. Liu, X. Luo and F. Wu, Organic small molecular nanoparticles based on self-assembly of amphiphilic fluoroporphyrins for photo-dynamic and photothermal synergistic cancer therapy, Colloids Surf., B, 2019, 182, 110345.
C.-L. Peng, P.-S. Lai, C.-C. Chang, P.-J. Lou and M.-J. Shieh, The synthesis and photodynamic properties of meso-sub-stituted, cationic porphyrin derivatives in HeLa cells, Dyes Pigm., 2010, 84(1), 140–147.
S. Yao, Y. Zheng, L. Jiang, C. Xie, F. Wu, C. Huang, X. Zhang, K.-L. Wong, Z. Li and K. Wang, Methylene violet 3RAX-conjugated porphyrin for photodynamic therapy: synthesis, DNA photocleavage, and cell study, RSC Adv., 2018, 8(8), 4472–4477.
L. Chen, Y. Zhao, X. Sun, J. Jiang, F. Wu and K. Wang, Synthesis, singlet oxygen generation and DNA photoclea-vage of β,β’-conjugated polycationic porphyrins, J. Porphyrins Phthalocyanines, 2019, 23(6), 655–663.
J. Zhang, C. Yang, R. Zhang, R. Chen, Z. Zhang, W. Zhang, S. H. Peng, X. Chen, G. Liu, C. S. Hsu and C. S. Lee, Biocompatible D-A Semiconducting Polymer Nanoparticle with Light-Harvesting Unit for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy, Adv. Funct. Mater., 2017, 27, 1605094.
J. M. Dąbrowski, B. Pucelik, M. M. Pereira, L. G. Arnaut and G. Stochel, Towards tuning PDT relevant photosensitizer properties: comparative study for the free and Zn2+ coordinated meso-tetrakis[2,6-difluoro-5-(N-methylsulfamylo) phenyl]porphyrin, J. Coord. Chem., 2015, 68, 3116–3134.
H. Huang, W. Song, J. Rieffel and J. F. Lovell, Emerging applications of porphyrins in photomedicine, Front. Phys., 2015, 3, 23.
M. Yang, J. Deng, D. Guo, Q. Sun, Z. Wang, K. Wang and F. Wu, Mitochondria-targeting Pt/Mn porphyrins as efficient photosensitizers for magnetic resonance imaging and photodynamic therapy, Dyes Pigm., 2019, 166, 189–195.
M. Yang, J. Deng, D. Guo, J. Zhang, L. Yang and F. Wu, A folate-conjugated platinum porphyrin complex as a new cancer-targeting photosensitizer for photodynamic therapy, Org. Biomol. Chem., 2019, 17(21), 5367–5374.
A. Naik, R. Rubbiani, G. Gasser and B. Spingler, Visible-light-induced annihilation of tumor cells with platinum-porphyrin conjugates, Angew. Chem., Int. Ed., 2014, 53(27), 6938–6941.
B. Marydasan, A. K. Nair and D. Ramaiah, Optimization of triplet excited state and singlet oxygen quantum yields of picolylamine-porphyrin conjugates through zinc insertion, J. Phys. Chem. B, 2013, 117(43), 13515–13522.
F. Wu, M. Yang, J. Zhang, S. Zhu, M. Shi and K. Wang, Metalloporphyrin-indomethacin conjugates as new photo-sensitizers for photodynamic therapy, J. Biol. Inorg. Chem., 2019, 24(1), 53–60.
J. S. Lindsey, I. C. Schreiman, H. C. Hsu, P. C. Kearney and A. M. Marguerettaz, Rothemund and Adler-Longo Reactions Revisited: Synthesis of Tetraphenylporphyrins under Equilibrium Conditions, J. Org. Chem., 1987, 52(5), 827–836.
M. Yang, S. Cao, X. Sun, H. Su, H. Li, G. Liu, X. Luo and F. Wu, Self-Assembled Naphthalimide Conjugated Porphyrins Nanomaterials with D-A Structure for PDT/PTT Synergistic Therapy, Bioconjugate Chem., 2020, 31(3), 663–672.
S. Meng, Z. Xu, G. Hong, L. Zhao, Z. Zhao, J. Guo, H. Ji and T. Liu, Synthesis, Characterization and In Vitro Photodynamic Antimicrobial Activity of Basic Amino Acid-Porphyrin Conjugates, Eur. J. Med. Chem., 2015, 92, 35–48.
Author information
Authors and Affiliations
Corresponding author
Additional information
Electronic supplementary information (ESI) available. See DOI: 10.1039/c9pp00363k
Rights and permissions
About this article
Cite this article
Deng, J., Li, H., Yang, M. et al. Palladium porphyrin complexes for photodynamic cancer therapy: effect of porphyrin units and metal. Photochem Photobiol Sci 19, 905–912 (2020). https://doi.org/10.1039/c9pp00363k
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/c9pp00363k