4 research outputs found
Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections
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
Hypoxia-Directed and Self-Immolative Theranostic Agent: Imaging and Treatment of Cancer and Bacterial Infections
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
Near-Infrared Emitting Polymer Nanogels for Efficient Sentinel Lymph Node Mapping
Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic spread of primary tumor to regional lymph nodes in clinical practice. In this research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was developed. The NIR-emitting polymer nanoprobes were designed and synthesized by conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer nanogels. The NIR-PNG nanoprobes were found to be photostable compared with the IRDye800-free dye at room temperature. Upon intradermal injection of the NIR-PNG into the front paw of a mouse, the nanoprobes entered the lymphatic system and migrated to the axillary lymph node within 2 min. The NIR fluorescence signal intensity and retention time of NIR-PNG in the lymph node were superior to the corresponding properties of the IRDye800-free dye. A immunohistofluorescence study of the SLN resected under NIR imaging revealed that the NIR-PNG nanoprobes were predominantly co-localized with macrophages and dendritic cells. Intradermal injection of NIR-PNG nanoprobes into the thigh of a pig permitted real-time imaging of the lymphatic flow toward the SLN. The position of the SLN was identified within 1 min with the help of the NIR fluorescence images. Taken together, the experimental results demonstrating the enhanced photostability and retention time of the NIR-PNG provide strong evidence for the potential utility of these polymer probes in cancer surgery such as SLN mapping
Near-Infrared Emitting Polymer Nanogels for Efficient Sentinel Lymph Node Mapping
Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic spread of primary tumor to regional lymph nodes in clinical practice. In this research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was developed. The NIR-emitting polymer nanoprobes were designed and synthesized by conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer nanogels. The NIR-PNG nanoprobes were found to be photostable compared with the IRDye800-free dye at room temperature. Upon intradermal injection of the NIR-PNG into the front paw of a mouse, the nanoprobes entered the lymphatic system and migrated to the axillary lymph node within 2 min. The NIR fluorescence signal intensity and retention time of NIR-PNG in the lymph node were superior to the corresponding properties of the IRDye800-free dye. A immunohistofluorescence study of the SLN resected under NIR imaging revealed that the NIR-PNG nanoprobes were predominantly co-localized with macrophages and dendritic cells. Intradermal injection of NIR-PNG nanoprobes into the thigh of a pig permitted real-time imaging of the lymphatic flow toward the SLN. The position of the SLN was identified within 1 min with the help of the NIR fluorescence images. Taken together, the experimental results demonstrating the enhanced photostability and retention time of the NIR-PNG provide strong evidence for the potential utility of these polymer probes in cancer surgery such as SLN mapping