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Synthesis and antitumor activity evaluation of a novel porphyrin derivative for photodynamic therapy in vitro and in vivo

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Tumor Biology

Abstract

A novel porphyrin derivative, 5, 10, 15, 20-tetrakis (5-morpholinopentyl)-21H, 23H-Porphin (MPP, 4) and its photophysical characteristics, therapeutic efficacy of photodynamic therapy (PDT) in vitro and in vivo, tumor selectivity, and clearance from normal tissues were investigated here. MPP has strong absorption at relatively long wavelength (λmax = 648 nm, molar absorption coefficient ε ∼ 17,200 M−1cm−1) and can emit strong fluorescence at 653 and 718 nm. When administered to the animal tumor models by tail vein injection, MPP was capable of accumulating in the tumor site, as examined in vivo with the fluorescence signal of MPP. By the combination of MPP and a 650-nm laser irradiation, the viability of T24 cells could decrease by 4.37 %, and inhibition rate of T24 tumor could increase up to 91.21 % compared with control group, demonstrating the potential of MPP as an effective photosensitizer in PDT for tumor treatment.

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Abbreviations

MPP 5:

10, 15, 20-tetrakis (5-morpholinopentyl)-21H, 23H-Porphin

PDT:

Photodynamic therapy

ros:

Reactive oxygen species

O2 :

Singlet oxygen

DPBF:

1, 3-diphenylisobenzofuran

DMSO:

Dimethyl sulfoxide

DMF:

N, N-dimethylformamide

PBS:

Phosphate buffered saline

T24:

Cell human bladder cancer cell line

FBS:

Fetal bovine serum

H&E:

Hematoxylin-eosin

MTT:

3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide

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Acknowledgments

This work was supported by Chinese National Natural Science Foundation (No. 21372042, 21402236, 81301878), Foundation of Shanghai government (No.14431906200, 14140903500, 13431900700, 13430722300, 13ZR1441000, 13ZR1440900, 14ZR1439800, 14ZR1439900, 15ZR1439900, 15XD1523400, 14SJGGYY08, 201370), International Cooperation Foundation of China and Croatia (6–11) and Foundation of Yiwu Science and Technology Bureau (No. 2012-G3-02, 2013-G3-03).

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Authors and Affiliations

  1. Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China

    Li-Jun Zhang, Ping-Yong Liao, Li Wang & Zhi-Long Chen

  2. Ningbo Dongmi Pharmaceutical Co. Ltd, Ningbo, Zhejiang, 315800, China

    Yi-Jia Yan

  3. Division of organic chemistry and biochemistry, Rudjer Boskovic Institute, Zagreb, Croatia

    Davor Margetic

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  1. Li-Jun Zhang
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Correspondence to Zhi-Long Chen.

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Zhang, LJ., Yan, YJ., Liao, PY. et al. Synthesis and antitumor activity evaluation of a novel porphyrin derivative for photodynamic therapy in vitro and in vivo. Tumor Biol. 37, 6923–6933 (2016). https://doi.org/10.1007/s13277-015-4576-7

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