A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor

Yuzhi Wang; Zhaohai Pan; Xiao Lan Cheng; Kai Zhang; Xin Zhang; Yao Qin; Jiaojiao Fan; Ting Yan; Tao Han; Kwok Keung Shiu; Sam Chun-Kit Hau; Nai Ki Mak; Daniel W J Kwong; Xiaona Liu; Minjing Li; Guowei Deng; Qiusheng Zheng; Jun Lu; Defang Li

doi:10.1016/j.ejmech.2020.112867

A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor

Yuzhi Wang, Zhaohai Pan, Xiao Lan Cheng, Kai Zhang, Xin Zhang, Yao Qin, Jiaojiao Fan, Ting Yan, Tao Han, Kwok Keung Shiu, Sam Chun-Kit Hau, Nai Ki Mak, Daniel W J Kwong, Xiaona Liu, Minjing Li, Guowei Deng, Qiusheng Zheng, Jun Lu^*, Defang Li^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

11 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is an emerging alternative cancer treatment modality that utilizes photo-sensitivity to cause cell death upon photo-irradiation. However, PDT efficiency has been hampered by tumor hypoxia, blue-shifted excitation wavelengths, and the high dark toxicity of photo-sensitizers. We designed and synthesized two novel porphycene-based photosensitizers (TBPoS-OH and TBPoS-2OH) with potent photo-cytotoxicity and a LD₅₀ in the nM range under both normoxic and hypoxic conditions in a variety of cell types after photo-irradiation (λ = 640 ± 15 nm). Further studies showed fast-cellular uptake for TBPoS-OH that localized lysosomes and subsequently induced cell apoptosis via the lysosomal-mitochondrial pathway. Moreover, TBPoS-OH significantly reduced tumor growth in two xenografted mouse models bearing melanoma A375 and B16 cells. Finally, TBPoS-OH exhibited no obvious immunogenicity and toxicity to blood cells and major organs in mice. These data demonstrated that these two porphycene-based photosensitizers, especially TBPoS-OH, could be developed as a potential PDT modality.

Original language	English
Article number	112867
Journal	European Journal of Medicinal Chemistry
Volume	209
Early online date	24 Sept 2020
DOIs	https://doi.org/10.1016/j.ejmech.2020.112867
Publication status	Published - 1 Jan 2021

Scopus Subject Areas

Pharmacology
Drug Discovery
Organic Chemistry

User-Defined Keywords

Hypoxic
Melanoma
Photodynamic therapy
Porphycene
Tumor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2020.112867

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Wang, Y., Pan, Z., Cheng, X. L., Zhang, K., Zhang, X., Qin, Y., Fan, J., Yan, T., Han, T., Shiu, K. K., Hau, S. C.-K., Mak, N. K., Kwong, D. W. J., Liu, X., Li, M., Deng, G., Zheng, Q., Lu, J., & Li, D. (2021). A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor. European Journal of Medicinal Chemistry, 209, Article 112867. https://doi.org/10.1016/j.ejmech.2020.112867

@article{832392c7287044728e4d644730cfb08e,

title = "A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor",

abstract = "Photodynamic therapy (PDT) is an emerging alternative cancer treatment modality that utilizes photo-sensitivity to cause cell death upon photo-irradiation. However, PDT efficiency has been hampered by tumor hypoxia, blue-shifted excitation wavelengths, and the high dark toxicity of photo-sensitizers. We designed and synthesized two novel porphycene-based photosensitizers (TBPoS-OH and TBPoS-2OH) with potent photo-cytotoxicity and a LD50 in the nM range under both normoxic and hypoxic conditions in a variety of cell types after photo-irradiation (λ = 640 ± 15 nm). Further studies showed fast-cellular uptake for TBPoS-OH that localized lysosomes and subsequently induced cell apoptosis via the lysosomal-mitochondrial pathway. Moreover, TBPoS-OH significantly reduced tumor growth in two xenografted mouse models bearing melanoma A375 and B16 cells. Finally, TBPoS-OH exhibited no obvious immunogenicity and toxicity to blood cells and major organs in mice. These data demonstrated that these two porphycene-based photosensitizers, especially TBPoS-OH, could be developed as a potential PDT modality.",

keywords = "Hypoxic, Melanoma, Photodynamic therapy, Porphycene, Tumor",

author = "Yuzhi Wang and Zhaohai Pan and Cheng, {Xiao Lan} and Kai Zhang and Xin Zhang and Yao Qin and Jiaojiao Fan and Ting Yan and Tao Han and Shiu, {Kwok Keung} and Hau, {Sam Chun-Kit} and Mak, {Nai Ki} and Kwong, {Daniel W J} and Xiaona Liu and Minjing Li and Guowei Deng and Qiusheng Zheng and Jun Lu and Defang Li",

note = "Funding Information: We acknowledge the financial support from the National Natural Science Foundation of China (Grant Nos. 81872162 and 81602556 to Defang Li, Grant No. 81803374 to Jun Lu, and Grant No. 31870338 to Qiusheng Zheng), Shandong Provincial Natural Science Foundation of China (Grant No. ZR2017JL030 to Defang Li), the Hong Kong Research Grants Council General Research Fund (GRF-HKBU 201312), Shenzhen science and technology innovation fund (Grant No. JCYJ20180302174121208 to Jun Lu), Key Research and Development Program of Shandong Province of China (Grant No. GG201809270118 to Qiusheng Zheng), HKBU Inter-institutional Collaborative Research Scheme (RC-ICRS/15?16/02D), Taishan Scholars Construction Engineering of Shandong Province (to Defang Li), Yantai High-End Talent Introduction Plan ?Double Hundred? (to Defang Li), the Scientific Research Foundation of Binzhou Medical University (Grant no. BY2016KYQD01 to Defang Li), and the Dominant Disciplines? Talent Team Development Scheme of Higher Education of Shandong Province (to Defang Li). Funding Information: We acknowledge the financial support from the National Natural Science Foundation of China (Grant Nos. 81872162 and 81602556 to Defang Li , Grant No. 81803374 to Jun Lu , and Grant No. 31870338 to Qiusheng Zheng), Shandong Provincial Natural Science Foundation of China (Grant No. ZR2017JL030 to Defang Li), the Hong Kong Research Grants Council General Research Fund ( GRF-HKBU 201312 ), Shenzhen science and technology innovation fund (Grant No. JCYJ20180302174121208 to Jun Lu), Key Research and Development Program of Shandong Province of China (Grant No. GG201809270118 to Qiusheng Zheng), HKBU Inter-institutional Collaborative Research Scheme ( RC-ICRS/15–16/02D ), Taishan Scholars Construction Engineering of Shandong Province (to Defang Li), Yantai High-End Talent Introduction Plan “Double Hundred” (to Defang Li), the Scientific Research Foundation of Binzhou Medical University (Grant no. BY2016KYQD01 to Defang Li), and the Dominant Disciplines{\textquoteright} Talent Team Development Scheme of Higher Education of Shandong Province (to Defang Li). Copyright {\textcopyright} 2020 Elsevier Masson SAS. All rights reserved.",

year = "2021",

month = jan,

day = "1",

doi = "10.1016/j.ejmech.2020.112867",

language = "English",

volume = "209",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson SAS",

}

Wang, Y, Pan, Z, Cheng, XL, Zhang, K, Zhang, X, Qin, Y, Fan, J, Yan, T, Han, T, Shiu, KK, Hau, SC-K, Mak, NK, Kwong, DWJ, Liu, X, Li, M, Deng, G, Zheng, Q, Lu, J & Li, D 2021, 'A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor', European Journal of Medicinal Chemistry, vol. 209, 112867. https://doi.org/10.1016/j.ejmech.2020.112867

TY - JOUR

T1 - A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor

AU - Wang, Yuzhi

AU - Pan, Zhaohai

AU - Cheng, Xiao Lan

AU - Zhang, Kai

AU - Zhang, Xin

AU - Qin, Yao

AU - Fan, Jiaojiao

AU - Yan, Ting

AU - Han, Tao

AU - Shiu, Kwok Keung

AU - Hau, Sam Chun-Kit

AU - Mak, Nai Ki

AU - Kwong, Daniel W J

AU - Liu, Xiaona

AU - Li, Minjing

AU - Deng, Guowei

AU - Zheng, Qiusheng

AU - Lu, Jun

AU - Li, Defang

N1 - Funding Information: We acknowledge the financial support from the National Natural Science Foundation of China (Grant Nos. 81872162 and 81602556 to Defang Li, Grant No. 81803374 to Jun Lu, and Grant No. 31870338 to Qiusheng Zheng), Shandong Provincial Natural Science Foundation of China (Grant No. ZR2017JL030 to Defang Li), the Hong Kong Research Grants Council General Research Fund (GRF-HKBU 201312), Shenzhen science and technology innovation fund (Grant No. JCYJ20180302174121208 to Jun Lu), Key Research and Development Program of Shandong Province of China (Grant No. GG201809270118 to Qiusheng Zheng), HKBU Inter-institutional Collaborative Research Scheme (RC-ICRS/15?16/02D), Taishan Scholars Construction Engineering of Shandong Province (to Defang Li), Yantai High-End Talent Introduction Plan ?Double Hundred? (to Defang Li), the Scientific Research Foundation of Binzhou Medical University (Grant no. BY2016KYQD01 to Defang Li), and the Dominant Disciplines? Talent Team Development Scheme of Higher Education of Shandong Province (to Defang Li). Funding Information: We acknowledge the financial support from the National Natural Science Foundation of China (Grant Nos. 81872162 and 81602556 to Defang Li , Grant No. 81803374 to Jun Lu , and Grant No. 31870338 to Qiusheng Zheng), Shandong Provincial Natural Science Foundation of China (Grant No. ZR2017JL030 to Defang Li), the Hong Kong Research Grants Council General Research Fund ( GRF-HKBU 201312 ), Shenzhen science and technology innovation fund (Grant No. JCYJ20180302174121208 to Jun Lu), Key Research and Development Program of Shandong Province of China (Grant No. GG201809270118 to Qiusheng Zheng), HKBU Inter-institutional Collaborative Research Scheme ( RC-ICRS/15–16/02D ), Taishan Scholars Construction Engineering of Shandong Province (to Defang Li), Yantai High-End Talent Introduction Plan “Double Hundred” (to Defang Li), the Scientific Research Foundation of Binzhou Medical University (Grant no. BY2016KYQD01 to Defang Li), and the Dominant Disciplines’ Talent Team Development Scheme of Higher Education of Shandong Province (to Defang Li). Copyright © 2020 Elsevier Masson SAS. All rights reserved.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Photodynamic therapy (PDT) is an emerging alternative cancer treatment modality that utilizes photo-sensitivity to cause cell death upon photo-irradiation. However, PDT efficiency has been hampered by tumor hypoxia, blue-shifted excitation wavelengths, and the high dark toxicity of photo-sensitizers. We designed and synthesized two novel porphycene-based photosensitizers (TBPoS-OH and TBPoS-2OH) with potent photo-cytotoxicity and a LD50 in the nM range under both normoxic and hypoxic conditions in a variety of cell types after photo-irradiation (λ = 640 ± 15 nm). Further studies showed fast-cellular uptake for TBPoS-OH that localized lysosomes and subsequently induced cell apoptosis via the lysosomal-mitochondrial pathway. Moreover, TBPoS-OH significantly reduced tumor growth in two xenografted mouse models bearing melanoma A375 and B16 cells. Finally, TBPoS-OH exhibited no obvious immunogenicity and toxicity to blood cells and major organs in mice. These data demonstrated that these two porphycene-based photosensitizers, especially TBPoS-OH, could be developed as a potential PDT modality.

AB - Photodynamic therapy (PDT) is an emerging alternative cancer treatment modality that utilizes photo-sensitivity to cause cell death upon photo-irradiation. However, PDT efficiency has been hampered by tumor hypoxia, blue-shifted excitation wavelengths, and the high dark toxicity of photo-sensitizers. We designed and synthesized two novel porphycene-based photosensitizers (TBPoS-OH and TBPoS-2OH) with potent photo-cytotoxicity and a LD50 in the nM range under both normoxic and hypoxic conditions in a variety of cell types after photo-irradiation (λ = 640 ± 15 nm). Further studies showed fast-cellular uptake for TBPoS-OH that localized lysosomes and subsequently induced cell apoptosis via the lysosomal-mitochondrial pathway. Moreover, TBPoS-OH significantly reduced tumor growth in two xenografted mouse models bearing melanoma A375 and B16 cells. Finally, TBPoS-OH exhibited no obvious immunogenicity and toxicity to blood cells and major organs in mice. These data demonstrated that these two porphycene-based photosensitizers, especially TBPoS-OH, could be developed as a potential PDT modality.

KW - Hypoxic

KW - Melanoma

KW - Photodynamic therapy

KW - Porphycene

KW - Tumor

UR - http://www.scopus.com/inward/record.url?scp=85091768978&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2020.112867

DO - 10.1016/j.ejmech.2020.112867

M3 - Journal article

C2 - 33010634

AN - SCOPUS:85091768978

SN - 0223-5234

VL - 209

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

M1 - 112867

ER -

A red-light-activated sulfonamide porphycene for highly efficient photodynamic therapy against hypoxic tumor

Abstract

Scopus Subject Areas

User-Defined Keywords

UN SDGs

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