High α-lipoic acid-loaded hollow mesoporous prussian blue nanozymes for targeted therapy of nasopharyngeal carcinoma in mice

Abstract

This study successfully constructs a tumor-targeting α-lipoic acid-loaded hollow mesoporous prussian blue nanozyme (AHPRzyme) for targeted therapy of nasopharyngeal carcinoma in mice. In these nanozymes, Arg-Gly-Asp (RGD) acts as a targeting ligand, enabling effective targeting of tumor cells. Additionally, AHPRzyme exhibits multiple anti-tumor mechanisms: ① The prussian blue nanozymes in AHPRzyme have catalase (CAT) activity, which decomposes H₂O₂ in human nasopharyngeal carcinoma CEN2 cells into non-toxic H₂O, reducing H₂O₂ levels and minimizing damage to normal cells. The released O₂ helps alleviate the hypoxic environment of the tumor, inhibiting lactate production due to hypoxia and consequently suppressing tumor growth. ② The prussian blue nanozymes also have peroxidase (POD) activity, which catalyzes H₂O₂ in tumor cells to generate ·OH, a reactive oxygen species, leading to tumor cell apoptosis. ③ The α-lipoic acid structure in AHPRzyme contains disulfide bonds that react with GSH, depleting excess glutathione (GSH) in tumor cells, disrupting the oxidative stress balance within the cells, and making them more sensitive to reactive oxygen species, thereby increasing tumor cell apoptosis. In summary, AHPRzyme can inhibit tumor cell growth and promote tumor cell apoptosis by improving the tumor microenvironment, achieving the goal of anti-nasopharyngeal carcinoma therapy.

Graphical Abstract