Synergistic Cancer Therapy: An NIR-Activated Methylene Blue-Nitrogen Mustard Prodrug for Combined Chemotherapy and Photodynamic Therapy

Nitrogen mustard, a widely used chemotherapeutic agent
for more
than 70 years, exhibits significant efficacy. However, its clinical
applications are severely limited by poor tumor selectivity and severe
side effects on normal tissues. To address these limitations, we developed
a near-infrared (NIR)-activatable nitrogen mustard prodrug, MBNM. Upon NIR irradiation, the controlled cleavage of the
urea bond within MBNM facilitates the simultaneous release
of nitrogen mustard and methylene blue (MB), enabling a synergistic
approach combining chemotherapy and photodynamic therapy (PDT) for
effective tumor suppression. Moreover, the release of MB upon activation
enables real-time monitoring of prodrug activation. Notably, MBNM demonstrated significantly improved biosafety compared
to free nitrogen mustard. These findings suggest that the photocleavable
prodrug MBNM offers a promising strategy for safe and
effective combination cancer therapy.