Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections.
Sanu KaranMi Young ChoHyunseung LeeHyun Min KimHye Sun ParkEun Hee HanJonathan L SesslerKwan Soo HongPublished in: Journal of medicinal chemistry (2023)
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-NO 2 , 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-NO 2 produces a distinct "fluorescence-on" signal, enabling real-time drug release monitoring. By leveraging elevated nitroreductase in cancer cells, NR-NO 2 gives rise to heightened bacterial cytotoxicity while sparing normal cells. In A549 solid tumor-bearing mice, NR-NO 2 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-NO 2 as a promising cancer therapy prodrug that benefits from targeted release, antibacterial impact, and imaging-based guidance.
Keyphrases
- cancer therapy
- drug release
- drug delivery
- papillary thyroid
- high resolution
- single molecule
- squamous cell
- type diabetes
- squamous cell carcinoma
- adipose tissue
- cell proliferation
- anti inflammatory
- childhood cancer
- cell cycle arrest
- climate change
- silver nanoparticles
- human health
- combination therapy
- minimally invasive
- free survival
- multidrug resistant