Spiky Cascade Biocatalysts as Peroxisome-Mimics for Ultrasound-Augmented Tumor Ablation

Abstract

Ultrasound (US)-augmented tumor ablation with sono-catalysts has emerged as a promising therapeutic modality due to high tissue penetration, nonionizing performance, and low cost of US-based therapies. Developing peroxisome-mimetic cascade biocatalysts for US-augmented synergistic treatment would further effectively reduce the dependence of the microenvironment H2O2 and enhance the tumor-localized reactive oxygen species (ROS) generation. Here, we proposed and synthesized a novel spiky cascade biocatalyst as peroxisome-mimics that consist of multiple enzyme-mimics, i.e., glucose oxidase-mimics (Au nanoparticles for producing H2O2) and heme-mimetic atomic catalytic centers (Fe-porphyrin for ROS generation), for US-augmented cascade-catalytic tumor therapy. The synthesized spiky cascade biocatalysts exhibit an obvious spiky structure, uniform nanoscale size, independent of endogenous H2O2, and efficient US-responsive biocatalytic activities. The enzyme-mimetic biocatalytic experiments show that the spiky cascade biocatalysts can generate abundant ·OH via a cascade chemodynamic path and also 1O2 via US excitation. Then, we demonstrate that the spiky cascade biocatalysts show highly efficient ROS production to promote melanoma cell apoptosis under US irradiation without extra H2O2. Our in vivo animal data further reveal that the proposed US-assisted chemodynamic cascade therapies can significantly augment the therapy efficacy of malignant melanoma. We suggest that these efficient peroxisome-mimetic cascade-catalytic strategies will be promising for clinical tumor therapies.

Piezoelectric Metal–Organic Frameworks Based Sonosensitizer for Enhanced Nanozyme Catalytic and Sonodynamic Therapies

“…Bioactive Au NPs are good nanozymes that exhibit intrinsic enzyme activities of catalase and peroxidase. 32 Au NPs can not only promote the charge separation and inhibit charge recombination but also change the charge distribution of UIO-66. As shown in Figure 1, UIO-66 NPs were synthesized through a hydrothermal reaction.…”

“…In this study, a combination of UIO-66 and Au nanoparticles (UIO-66-Au NPs) as piezoelectric sonosensitizers is proposed. Bioactive Au NPs are good nanozymes that exhibit intrinsic enzyme activities of catalase and peroxidase . Au NPs can not only promote the charge separation and inhibit charge recombination but also change the charge distribution of UIO-66.…”

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

“…However, these small porphyrins are less chemically and biologically stable and require further optimization. A series of recent studies have found that metalloporphyrin complexes can optimize these properties 112 . For instance, Liu's group had designed a multifunctional nanoplatform (named R-S-NTP) based on Fe (III), meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS), Bis (DPA-Zn)-RGD, and manganese superoxide dismutase (SOD 2 , an important antioxidant enzyme) siRNA for enhancing the production of ROS through targeted delivery and triple regulation methods, including SOD 2 down-regulation, glutathione depletion and Fenton reaction ( Figure 4 A ).…”

Advances in the Application of Nanomaterials to the Treatment of Melanoma

“…Moreover, Yuan et al proposed and synthesized a novel doping cascade biocatalyst as a peroxisome mimetic, consisting of several enzyme mimetics, such as glucose oxidase mimics (Au nanoparticles for producing H 2 O 2 ) and heme-mimetic atomic catalytic centers (Fe-porphyrin for ROS generation). The synthesized doping cascade biocatalysts suggested that the therapeutic effect of malignant melanoma can be significantly enhanced in in vivo animal data [ 108 ].…”