The ZIF-8 nanoplatform targeted delivery of IFI44 siRNA to suppress bladder cancer development via modulating the PI3K/AKT signaling pathway

Malignant progression of bladder cancer (BC) is frequently caused by its complex molecular regulation, leading to unfavorable clinical outcomes. Our research indicates that interferon-induced protein 44 (IFI44) is significantly overexpressed in BC, thereby facilitating its malignant progression. Mechanistically, BC's progression is impeded by the knockdown of IFI44, partially due to the inhibition of the PI3K/AKT signaling pathway. In addition, we constructed a Zeolitic Imidazolate Framework-8 (ZIF-8) nanoplatform, incorporating ZIF-8@siIFI44, ZIF-8@siIFI44@PEG and ZIF-8@siIFI44@PEG-RGD. Subsequent experiments demonstrated that ZIF-8@siIFI44 and ZIF-8@siIFI44@PEG possess anti-tumor property, while ZIF-8@siIFI44@PEG-RGD exhibited enhanced anti-tumor efficacy due to the inclusion of RGD targeting peptides which especially target tumors. Additionally, our study confirmed that the ZIF-8 nanoplatform enables targeted delivery of IFI44 siRNA, therefore preventing BC development partially by influencing the PI3K/AKT signaling pathway. Our findings identify IFI44 as an element that aids in the malignant development of BC, emphasizing its promise as a target for therapy.