Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections

  • J Med Chem. 2023 Oct 26;66(20):14175-14187. doi: 10.1021/acs.jmedchem.3c01274.
Sanu Karan  1 ,  Mi Young Cho  1 ,  Hyunseung Lee  1 ,  Hyun Min Kim  1 ,  Hye Sun Park  1 ,  Eun Hee Han  1 ,  Jonathan L Sessler  2 ,  Kwan Soo Hong  1  3  4
Affiliations
  • 1. Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
  • 2. Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712-1224, United States.
  • 3. Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Republic of Korea.
  • 4. Department of Chemistry, Chung-Ang University, Seoul 06974, Republic of Korea.
PMID: 37823731 DOI: 10.1021/acs.jmedchem.3c01274
Abstract

The impact of bacteria on Cancer progression and treatment is becoming increasingly recognized. Cancer-associated bacteria are linked to metastases, reduced efficacy, and survival challenges. In this study, we present a sensitive hypoxia-activated prodrug, NR-NO2, which comprises an Antibiotic combined with a chemotherapeutic. This prodrug demonstrates rapid and robust fluorescence enhancement and exhibits potent Antibacterial activity against both Gram-positive and Gram-negative bacteria as well as tumor cells. Upon activation, NR-NO2 produces a distinct "fluorescence-on" signal, enabling real-time drug release monitoring. By leveraging elevated nitroreductase in Cancer cells, NR-NO2 gives rise to heightened Bacterial cytotoxicity while sparing normal cells. In A549 solid tumor-bearing mice, NR-NO2 selectively accumulated at tumor sites, displaying fluorescence signals under hypoxia superior to those of a corresponding prodrug-like control. These findings highlight the potential of NR-NO2 as a promising Cancer therapy prodrug that benefits from targeted release, Antibacterial impact, and imaging-based guidance.

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