Nanozyme with Robust Catalase Activity by Multiple Mechanisms and Its Application for Hypoxic Tumor Treatment

Abstract

Utilizing catalase-mimicking nanozymes to produce O 2 is an effective method to overcome tumor hypoxia. However, it is challenging to fabricate nanozymes with ultrahigh catalytic activity. Palladium nanosheet (Pd NS), a photothermal agent for photothermal therapy (PTT), has superior catalase-mimicking activity. Here, titanium dioxide (TiO 2 ) is used to modify Pd NS (denoted Pd@TiO 2 ) by a simple one-step method to improve its catalytic activity about 8 times. The enhancement mechanism's fundamental insights are discussed through experiments and density functional theory calculations. Next, zinc phthalocyanine is loaded on Pd@TiO 2 to form a nanomotor (denoted PTZCs) with the synergistic activities of photodynamic therapy and PTT. PTZCs inherit the catalase activity of Pd@TiO 2 to facilitate the decomposition of endogenous H 2 O 2 to O 2 , which can relieve tumor hypoxia and propel PTZC migration to expand the reach of PTZCs, further enhancing its synergistic treatment outcome both in vitro and in vivo. It is proposed that this work can provide a simple and effective strategy for catalytic activity enhancement and bring a critical new perspective to studying and guiding the nanozyme design.

Nanozymes: Versatile Platforms for Cancer Diagnosis and Therapy

“…To mimic the enzymatic activity of CAT, many metalcontaining and carbon-based nanomaterials have been developed [83][84][85][86][87][88][89][90][91]. For instance, Dan and coworkers designed indocyanine green-loaded ultrasmall gold nanoclusters (Au NCs-ICG) that had a similar catalytic capability to CAT but not POD or SOD (Fig.…”

Catalase‐Like Nanozymes: Classification, Catalytic Mechanisms, and Their Applications

“…By comparing the decomposition of H 2 O 2 on Pd NS and Pd@TiO 2 , it is found that the decomposition of H 2 O 2 on Pd@TiO 2 releases more heat and has higher activity. [78] To sum up, the catalytic reaction mechanisms of H 2 O 2 decomposition catalyzed by metal and metal oxides as CAT-like nanozymes are presented. The catalytic mechanisms of CAT-like enzymes can be divided into homolytic and heterolytic paths, which are determined by RDS.…”

“…Utilizing intrinsic CAT-like activity, PTZCs catalyze the decomposition of H 2 O 2 to O 2 , thereby improving tumor hypoxia and further enhancing the synergistic efficiency of PTT and PDT both in vivo and in vitro. [78] For enhancing combination of PDT/PTT tumor therapy, Li et al synthesized Pt-Ce6 nanocomposites. It has been demonstrated that this versatile Pt-Ce6 nanoplatform exhibits superior CATlike activity, thus continuously and stably decompose H 2 O 2 into oxygen, thereby alleviating tumor hypoxia and improving the synergistic therapeutic effect of PDT and PTT in vitro or in vivo.…”

Recent Advances in Strategies for Addressing Hypoxia in Tumor Photodynamic Therapy

“…Recently, the employment of metal-based materials to promote the decomposition of tumor endogenous H 2 O 2 to generate oxygen has attracted increasing attention. Titanium dioxide-modified palladium (Pd) nanosheets [ 123 ], Pd nanoparticles [ 124 ], defective cobalt (Co) hydroxide [ 125 ], Co 3 O 4 nanoparticles [ 126 ], iridium (Ir) oxide [ 127 , 128 ], cerium (Ce) oxide nanoparticles [ 129 , 130 ], platinum (Pt) nanozyme [ 131 , 132 ], gold (Au) nanoclusters [ 133 ], iron (Fe)-based materials [ 134 , 135 , 136 , 137 , 138 ], etc. have been used to accelerate the decomposition of H 2 O 2 to generate oxygen.…”