Hollow Nanooxidase Enhanced Phototherapy Against Solid Tumors.

ABSTRACT

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 ∼160 nm were synthesized via a two-step process of coprecipitation and etching. These NCs can react with O2 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-1H-imidazol-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.