Hollow Nanooxidase Enhanced Phototherapy Against Solid Tumors

Although phototherapy has attracted extensive attention in antitumor field in recent years, its therapeutic effect is usually unsatisfactory because of the complexity and variability of the tumor microenvironment (TME). Herein, we report novel CoSn(OH)(6)@CoOOH hollow carriers with oxidase properties that can enhance phototherapy. Hollow CoSn(OH)(6)@CoOOH nanocubes (NCs) with a particle size of similar to 160 nm were synthesized via a two-step process of coprecipitation and etching. These NCs can react with O-2 to generate singlet oxygen without hydrogen peroxide and consume glutathione, and their hollow structure can be utilized to carry drug molecules. After loading indocyanine green (ICG) and 1,2-bis(2-(4,5-dihydro-1Himidazol-2-yl)propan-2-yl) diazene dihydrochloride (AIPH), the resulting nanosystem (HCIA) exhibited enhanced phototherapy effects through the catalytic activity of oxidase, production of alkyl radicals, and consumption of glutathione. Cell and mouse experiments showed that HCIA combined with near-infrared laser irradiation significantly inhibited the growth of 4T1 tumors. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that PI3K-Akt and MAPK signaling pathways were highly relevant to this therapeutic system. Such hollow NCs with oxidase activity have considerable potential for the design of multifunctional drug delivery vehicles for tumor therapy.

Automated summary

Although phototherapy has been extensively studied in recent years, its efficacy in treating tumors is often unsatisfactory due to the complex and variable tumor microenvironment. In this study, we report the discovery of novel hollow carriers named CoSn(OH)6@CoOOH with oxidase properties, which can enhance the effectiveness of phototherapy. These carriers react with oxygen to generate singlet oxygen and consume glutathione, and their hollow structure allows for the delivery of drug molecules. Loading indocyanine green and AIPH onto the carriers resulted in enhanced phototherapy effects through oxidase-catalyzed reactions, generation of alkyl radicals, and glutathione consumption. Cell and mouse experiments demonstrated that these carriers, combined with near-infrared laser irradiation, significantly inhibited tumor growth. Enrichment analysis revealed the involvement of the PI3K-Akt and MAPK signaling pathways in this therapeutic system. Hollow carriers with oxidase activity like these have great potential for the design of multifunctional drug delivery vehicles for tumor therapy.