Dual-targeting nanozyme for tumor activatable photo-chemodynamic theranostics

Tumor phototheranostics holds a great promise on account of its high spatiotemporal resolution, tumor-specificity, and noninvasiveness. However, physical limitation of light penetration and always on properties of conventional photothermal-conversion agents usually cause difficulty in accurate diagnosis and completely elimination of tumor. Meanwhile, nanozymes mediated Fenton reactions can well utilize the tumor microenvironment (TME) to generate hydroxyl radicals for chemodynamic therapy (CDT), but limited by the concentration of H2O2 in TME and the delivery efficiency of nanozymes. To overcome these problems, a dual-targeting nanozyme (FTRNPs) is developed for tumor-specific in situ theranostics, based upon the assembling of ultrasmall Fe3O4 nanoparticles, 3,3',5,5'-tetrameth-ylbenzidine (TMB) and the RGD peptide. The FTRNPs after H2O2 treatment exhibits superior photothermal stability and high photothermal conversion efficiency (n = 50.9%). FTRNPs shows extraordinary accumulation and retention in the tumor site by biological/physical dual-targeting, which is 3.54-fold higher than that without active targeting. Cascade-dual-response to TME for nanozymes mediated Fenton reactions and TMB oxidation further improves the accuracy of both photoacoustic imaging and photothermal therapy (PTT). The tumor inhibition rate of photo-chemodynamic therapy is similar to 97.76%, which is similar to 4-fold higher than that of PTT or CDT only. Thus, the combination of CDT and PTT to constructturn on nanoplatform is of great significance to overcome their respective limitations. Considering its optimized all-in-one performance, this new nanoplatform is expected to provide an advanced theranostic strategy for the future treatment of cancers.

Automated summary

Tumor phototheranostics has great potential due to its high spatiotemporal resolution, tumor-specificity, and noninvasiveness. The authors developed a dual-targeting nanozyme with excellent photothermal stability and high photothermal conversion efficiency. The nanozyme showed superior accumulation and retention at the tumor site through biological/physical dual-targeting. The combined effect of the nanozyme improved the accuracy of both photoacoustic imaging and photothermal therapy. The tumor inhibition rate of the photo-chemodynamic therapy was 4-fold higher than that of photothermal therapy or chemodynamic therapy alone.