Nitric oxide (NO) is a crucial gaseous medium for
tumor growth and progression, but it may also cause
mitochondrial disorder and DNA damage by drastically increasing its concentration in
tumor. Due to its challenging administration and unpredictable release, NO based gas
therapy is difficult to eliminate malignant
tumor at low safe doses. To address these issues, herein, we develop a multifunctional nanocatalyst called Cu-doped
polypyrrole (CuP) as an intelligent nanoplatform (CuP-B@P) to deliver the NO precursor BNN6 and specifically release NO in
tumors. Under the aberrant metabolic environment of
tumors, CuP-B@P catalyzes the conversion of
antioxidant GSH into
GSSG and excess H2O2 into ·OH through Cu+/Cu2+ cycle, which results in oxidative damage to
tumor cells and the concomitant release of cargo BNN6. More importantly, after
laser exposure, nanocatalyst CuP can absorb and convert photons into
hyperthermia, which in turn, accelerates the aforesaid catalytic efficiency and pyrolyzes BNN6 into NO. Under the synergistic effect of
hyperthermia, oxidative damage, and NO burst, almost complete
tumor elimination is achieved in vivo with negligible toxicity to body. Such an ingenious combination of NO
prodrug and nanocatalytic medicine provides a new insight into the development of NO based therapeutic strategies. STATEMENT OF SIGNIFICANCE: A
hyperthermia-responsive NO delivery nanoplatform (CuP-B@P) based on Cu-doped
polypyrrole was designed and fabricated, in which CuP catalyzed the conversion of H2O2 and GSH into ·OH and
GSSG to induce intratumoral oxidative damage. After
laser irradiation,
hyperthermia ablation and responsive release of NO further coupled with oxidative damage to eliminate malignant
tumors. This versatile nanoplatform provides new insights into the combined application of catalytic medicine and gas
therapy.