Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections
Sanu Karan, Mi Young Cho, Hyun-Seung Lee, Hyun Min Kim, Hye Sun Park, Eun Hee Han, Jonathan L. Sessler, Kwan Soo Hong
Abstract
High Resolution Image Download MS PowerPoint Slide 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.