SCIENCE CHINA Materials, Volume 62, Issue 8: 1199-1209(2019) https://doi.org/10.1007/s40843-019-9423-5

A pH-responsive zinc (II) metalated porphyrin for enhanced photodynamic/photothermal combined cancer therapy

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  • ReceivedJan 9, 2019
  • AcceptedMar 26, 2019
  • PublishedApr 12, 2019


The acidic tumor microenvironment is triggered by glycolysis in hypoxic condition, which can motivate the pH-responsive system to build certain triggers for efficiently tumor-targeted phototherapy. Additionally, the metalated porphyrin structures are widely studied in biomedical applications due to the favorable properties of high singlet oxygen quantum yield as well as strong fluorescence imaging ability. Herein, a pH-responsive zinc (II) metalated porphyrin (P-4) was designed and synthesized for amplifying cancer photodynamic/photothermal therapy with excellent fluorescence quantum yield (67.4%), superb singlet oxygen quantum yield (84.3%) and desired photothermal conversion efficiency (30.0%). In vitro, the self-assembled P-4 nanoparticles can specifically target to lysosome subcellular site and realize protonated process of dibutaneaminophenyl (DBAP) groups with high photo toxicity. Under single 660 nm laser illumination, the tumor can be ablated completely with no side effects in vivo. This work demonstrates that the pH-responsive P-4 nanoparticles provide a new avenue for highly efficient cancer combination therapy.

Funded by

National Natural Science Foundation of China(61525402,61775095,21704043)

Jiangsu Provincial Key Research and Development Plan(BE2017741)

Six talent peak innovation team in Jiangsu Province(TD-SWYY-009)

and the Natural Science Foundation of Jiangsu Province(BK20170990,17KJB150020)


This work was supported by the National Natural Science Foundation of China (61525402, 61775095 and 21704043), Jiangsu Provincial Key Research and Development Plan (BE2017741), Six Talent Peak Innovation Team in Jiangsu Province (TD-SWYY-009), and the Natural Science Foundation of Jiangsu Province (BK20170990 and 17KJB150020).

Interest statement

The authors declare that they have no conflict of interest.

Contributions statement

Dong X designed the project. Dong X, Si W and Yang Z guided the project. Liang P and Tang H performed the experiments. Gu R, Xue L, Chen D and Wang W performed some supplemental experiments. Dong X, Si W and Liang P analyzed the results and wrote the manuscript. All authors participated in general discussion of the paper.

Author information

Pingping Liang is studying for a PhD degree at the Institute of Advanced Materials (IAM), Nanjing Tech University. Her research interest focuses on the cancer phototherapy.

Weili Si received her PhD degree in 2015, from Tohoku University, Japan. Then she joined the Institute of Advanced Materials, Nanjing Tech University as an associate professor. Her current research interests focus on the development of novel photosensitizers and the application in medicinal chemistry.

Xiaochen Dong obtained his PhD degree from Zhejiang University in China in 2007. Then he joined the School of Materials Science and Engineering in Nanyang Technological University as a postdoc. In 2012, he joined the Institute of Advanced Materials, Nanjing Tech University, as a Full Professor. He has published more than 200 papers, including those in Adv. Mater., ACS Nano, JACS, etc. His current research involves biophotonics and bioelectronics.


Supplementary information

The synthesis of N,N-dibutyl-4-ethynylaniline and supporting results are available in the online version of the paper.


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  • Figure 1

    (a) Proposed protonation mechanism of P-4 triggered by H+. (b–d) Color, absorbance and emission changes of P-4 solution (in DCM) with TFA addition.

  • Scheme 1

    Simplified representation of multi-imaging guided pH-responsive cancer PTT/PDT in vitro and in vivo with P-4 NPs.

  • Figure 2

    (a) Photographs of P-4 and P-4 NPs. (b) TEM image of P-4 NPs (pH 7.4), inset: DLS size distribution. (c, d) Absorbance of P-4 and P-4 NPs at different concentrations. (e) Fluorescence spectra of SOSG mixed with P-4 NPs (pH 7.4). (f, g) Photothermal curves of P-4 NPs at different concentrations and pH. (h) Heating and cooling curves of P-4 NPs (80 µg mL−1) for four cycles (660 nm, 0.8 W cm−2). (i) Photothermal curve of P-4 NPs (0.5 mL, 80 µg mL−1) during laser on and off (660 nm, 0.8 W cm−2, control: PBS).

  • Figure 3

    (a, b) MTT and flow cytometry assays (660 nm, 8 min, 0.8 W cm−2). (c, d) Fluorescence images (200×) of calcein-AM/PI co-staining HeLa cells incubated without and with P-4 NPs (660 nm, 10 min, 0.8 W cm−2, 16 µg mL−1).

  • Figure 4

    (a, b) Confocal fluorescence images of HeLa cells incubated with P-4 NPs (10 µg mL−1) and DCFH-DA after laser illumination. (c) Sub-cellular localization of P-4 NPs at pH 7.4 in HeLa cells. Scale bar: 10 µm; P-4 NPs and trackers were excited at 488 nm.

  • Figure 5

    (a) Fluorescence images of tumor and selected organs in tumor-bearing mice after intravenous injection of P-4 NPs. (b) Photothermal images of tumor-bearing mice in the absence and presence of P-4 NPs intravenous injection (80 µg mL−1, 100 µL). (c) Visual photographs of mice from three groups after 18 days treatment.

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