Alkaline Phosphatase Activated Near-Infrared Frequency Upconversion Photosensitizers for Tumor Photodynamic Therapy

  • J Med Chem. 2024 Aug 8;67(15):13383-13391. doi: 10.1021/acs.jmedchem.4c01296.
Chao Zhao  1 ,  Wanlu Sun  1 ,  Xiaoyan Huang  1 ,  Yi Liu  1 ,  Hai-Yan Wang  2
Affiliations
  • 1. School of Engineering, China Pharmaceutical University, Nanjing 211198, China.
  • 2. School of Mechanical Engineering, Southeast University, Nanjing 211189, China.
PMID: 39057921 DOI: 10.1021/acs.jmedchem.4c01296
Abstract

Photodynamic therapy (PDT) is a promising Anticancer method due to its noninvasive features, high efficiency, and superior accuracy. The activated near-infrared upconversion Photosensitizer has a high tissue penetration depth and could be explicitly released with minimal side effects. Therefore, we designed and synthesized a series of Br-substituted compounds (NFh-Br) based on the near-infrared upconversion hemicyanine dye. The heavy atomic effect improves the generation of 1O2 and upconversion luminous efficiency. Especially, NFh-Br11 exhibited an excellent 1O2 generation rate under 808 nm excitation and effectively killed tumor cells in vitro, and the Alkaline Phosphatase (ALP)-activatable Photosensitizer (NFh-ALP) was obtained by modifying the NFh-Br11. NFh-ALP could be activated by ALP and release NFh-Br11, which induces Apoptosis of tumor cells and has outstanding Anticancer effects in vitro and in vivo. This work could provide a strategy for designing activatable upconversion photosensitizers.

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