Pd@Ir-LOD multienzyme utilizing endogenous lactate consumption cooperates with photothermal for tumor therapy

• Published in: Nano research Vol. 17; no. 1; pp. 270 - 281
• Main Authors: Ye, Zichen, Li, Yun, Li, Jingchao, Hu, Xinyan, Zheng, Jinyang, Zhang, Gongxin, Xiang, Sijin, Zhu, Tianbao, Guo, Zhide, Chen, Xiaolan
• Format: Journal Article
• Language: English
• Published: Beijing Tsinghua University Press 2024; Springer Nature B.V
• Subjects: Accumulation; Acids; Apoptosis; Atomic/Molecular Structure and Spectra; Biocompatibility; Biomedicine; Biotechnology; Cancer therapies; Cascade chemical reactions; Catalase; Catalysis; Chemistry; Chemistry and Materials Science; Condensed Matter Physics; Consumption; Efficiency; Enzymes; Glucose; Glutathione; Hydrogen peroxide; Laboratories; Lactate oxidase; Lactic acid; Materials Science; Metabolism; Nanoparticles; Nanotechnology; Particle size; Peroxidase; Photothermal conversion; Reactive oxygen species; Research Article; Scavenging; Therapy; Tumor microenvironment; Tumors; lactate oxidase; tumor microenvironment; cascade reaction; chemodynamic therapy; photothermal therapy
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-023-5764-1

Lactic acid (LA) plays a major role in the occurrence, development, and spread of cancer. Enlightened by its high accumulation in tumor site, a novel lactate oxidase (LOD) conjugated two-dimensional Pd@Ir nanoplatform (Pd@Ir-LOD, PIL) was fabricated to combine cascade reaction with photothermal for tumor therapy. In detail, the overexpressed LA in tumor microenvironment (TME) was a key factor to activate the PIL-based cascade reaction: (1) Plenty of H
2
O
2
could be generated from LA by the catalysis of LOD with O
2
; (2) potent OH was produced from H
2
O
2
due to the peroxidase (POD)-like activity of PIL; (3) meantime, PIL’s catalase (CAT)-like activity could decompose part H
2
O
2
into O
2
to achieve the purpose of LA cyclic oxidization. Moreover, the reduced glutathione (GSH) scavenging capability of PIL might protect the produced reactive oxygen species (ROS) from being cleared to further improve the cascade therapeutic effect. More importantly, PIL had excellent photothermal conversion efficiency (37.35%) and manifested a surprising temperature rising effect in tumor. Taken together, the decreasing LA concentration, accumulation of high-toxic ROS, the depletion of GSH together with the higher intra-tumoral temperature potently enhanced
in vivo
antitumor therapy. Therefore, a promising therapeutic tactic based on PIL integrating endogenous LA consumption, chemodynamic therapy (CDT), and photothermal therapy (PTT) has been put forward.