A Hypoxia-Activated BODIPY-Azo Anticancer Prodrug for Bimodal Chemo-Photodynamic Therapy

For cancer treatment, collaborative strategies have been
the mainstream
for overcoming the restrictions resulting from monotherapy. Combining
chemotherapy with photodynamic therapy (PDT) has been shown to increase
the antitumor effect and reduce side impacts. This study reports a
hypoxia-activated prodrug BOD-Azo-single with a PDT agent and aniline
mustard connected by the azo bond. With light illumination, BOD-Azo-single
exhibited some PDT. Under hypoxic conditions, the azo bond cleaved
and released BOD-3-single of higher phototoxicity and aniline mustard
of chemotoxicity. In vivo therapeutic experiments
showed that BOD-Azo-single with light significantly reduced A375 tumor
proliferation with 92% TGI value. Overall, in this study, PDT was
employed to address the adverse systemic toxicity of chemotherapy
and the released chemotoxicity made up for the inefficiency of PDT
in the hypoxic tumor microenvironment, introducing a new strategy
for developing combined therapeutic agents to be advantageous to each
other. Under a hypoxic tumor environment, BOD-3-single and aniline
mustard exerted a strong synergistic effect (CI = 0.25), indicating
that BOD-Azo-single is a real bimodal chemo-photodynamic therapeutic
agent.