Catalytically Selective Chemotherapy from Tumor‐Metabolic Generated Lactic Acid

Abstract

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smll.201903746. Lactic acid (LA) is a powerful molecule as the metabolic driver in tumor microenvironments (TMEs). Inspired by its high intratumoral level(5-20 µmol g −1 ), a novel treatment paradigm via the cascade release of H 2 O 2 and ·OH from the LA generated by tumor metabolism is developed for catalytic and pH-dependent selective tumor chemotherapy. By utilizing the acidity and overexpression of LA within the TME, the constructed lactate oxidase (LOD)-immobilized Ce-benzenetricarboxylic acid (Ce-BTC) metal organic framework enables the intratumoral generation of ·OH via a cascade reaction: 1) the in situ catalytic release of H 2 O 2 from LA by LOD, and 2) the catalytic production of ·OH from H 2 O 2 by Ce-BTC with peroxidase-like activity. Highly toxic ·OH effectively induces tumor apoptosis/death. A new strategy for selective tumor chemotherapy is provided herein.

A pH‐Responsive Polymer‐CeO2 Hybrid to Catalytically Generate Oxidative Stress for Tumor Therapy

“…Various natural enzymes and nanocatalysts, such as lactate oxidase, glucose oxidase, and gold nanoparticles, have been employed as catalysts to elevate the intratumoral ROS level and then effectively induce tumor-cell death. [11][12][13][14][15][16][28][29][30][31][32] Previous investigations on the catalytic chemodynamic therapy mainly rely on the catalytic generation of OH as the active species to induce tumor cell death. Among various ROS in biological systems, superoxide anion (O 2…”

“…Various natural enzymes and nanocatalysts, such as lactate oxidase, glucose oxidase, and gold nanoparticles, have been employed as catalysts to elevate the intratumoral ROS level and then effectively induce tumor‐cell death. [ 11–16,28–32 ]…”

NIR Light‐Driven Bi2Se3‐Based Nanoreactor with “Three in One” Hemin‐Assisted Cascade Catalysis for Synergetic Cancer Therapy

“…More importantly, about 0.97 ± 0.04 and 0.71 ± 0.03 m m H 2 O 2 produced in the cells (1 × 10 6 ) treated with Bi 2 Se 3 @hemin‐HA NPs and Bi 2 Se 3 @hemin‐(G‐H)‐HA NPs, respectively. This was much higher than the H 2 O 2 concentration in the tumor cells (0.01–0.1 m m ) than that reported in the past literature, [ 49,52 ] which would radically accelerate CDT by increasing the substrate concentration.…”

“…Finally, the total ROS generation in each group was measured with DCFH‐DA probe, [ 49 ] to verify whether hemin assists Bi 2 Se 3 @hemin‐(G‐H)‐HA NPs to maximize its ROS generation. As revealed in Figure 3D, Bi 2 Se 3 @hemin‐(G‐H)‐HA NPs yielded the most amount of ROS, as the heterostructure separated the charge–hole pairs to increase the generation of H 2 O 2 , then that was catalyzed by aggregation‐limited hemin to produce highly active •OH and plenty of O 2 , which was further transformed into •O 2 − , completing the multi‐step cascade reactions (Figure 3H).…”

Engineering Biofunctional Enzyme‐Mimics for Catalytic Therapeutics and Diagnostics

“…Whether MOFs are used as matrixes or act as biocatalytic mimics, [ 157 ] their highly controllable bioactivity makes MOFs‐based Enz‐Ms have great potential for further application in nanomedicines and regenerative therapies. [ 158,159 ] To improve their biocatalytic efficiency in the biological system, the priority problem to be solved is the difference in optimal catalytic efficiencies between the in vitro pH conditions and the physiological pH environments. [ 160 ] Based on this, the Qu group designed a MOF‐based hybrid nanocatalyst to realize the best catalytic performance through cascade reactions.…”