Polyamine Derived Photosensitizer: A Novel Approach for Photodynamic Therapy of Cancer.

Hao Deng, Ke Xie, Liling Hu, Xiaowen Liu, Qingyun Li, Donghui Xie, Fengyi Xiang, Wei Liu, Weihong Zheng, Shuzhang Xiao, Jun Zheng, Xiao Tan
Author Information
  1. Hao Deng: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  2. Ke Xie: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  3. Liling Hu: The First College of Clinical Medical Science, China Three Gorges University, Yichang 443003, China.
  4. Xiaowen Liu: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  5. Qingyun Li: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  6. Donghui Xie: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  7. Fengyi Xiang: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  8. Wei Liu: The First College of Clinical Medical Science, China Three Gorges University, Yichang 443003, China.
  9. Weihong Zheng: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
  10. Shuzhang Xiao: College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
  11. Jun Zheng: The First College of Clinical Medical Science, China Three Gorges University, Yichang 443003, China.
  12. Xiao Tan: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.

Abstract

Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT.

Keywords

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Grants

  1. 81602743/National Natural Science Foundation of China
  2. SDHZ2021245, SDHZ20230118/Applied Natural Science Fund of China Three Gorges University
  3. 2023KZL02, 2022KZL2-06/Open Fund of Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University
  4. A21-2-003/Yichang Municipal Medical and Health Research Project Fund
  5. 2024AFD172/Hubei Provincial Natural Science Foundation for Innovative Development Joint Fund Project

MeSH Term

Photosensitizing Agents
Photochemotherapy
Animals
Mice
Humans
Polyamines
Cell Line, Tumor
Pancreatic Neoplasms
Cell Proliferation
Xenograft Model Antitumor Assays

Chemicals

Photosensitizing Agents
Polyamines

Word Cloud

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