Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a global health challenge. Small interfering RNA (siRNA) is a promising therapeutic modality that blocks multiple disease-causing genes without impairing cell structures. However, siRNA therapeutics still have off-target proportion and lack effective quantitative analysis method in vivo. Thus, a novel theragnostic nanoparticle with dual-mode imaging is synthesized for targeted and image-guided siRNA therapy of HCC. Survivin siRNA is carried by Poly-ethylenimine (PEI) and interacted with T7-AIE/Gd NPs, which are self-assembled of DSPE-PEG-DTPA(Gd), DSPE-PEG-Mal, DSPE-PEG-PEI, and TPE. The resulting theragnostic nanoparticles exhibit lower toxicity and high therapeutic effect, and excellent T1-weighted magnetic resonance imaging (MRI) and aggregation-induced emission (AIE) imaging performance. Moreover, in vivo MRI and AIE imaging indicate that this kind of theragnostic nanoparticles rapidly accumulates in the tumor due to active targeting and enhanced permeability and retention (EPR) effects. Sur@T7-AIE-Gd suppresses HCC tumor growth by inducing autophagy and destabilizes DNA integrity in tumor cells. The results suggest that T7-AIE-Gd nanoparticles carrying Survivin siRNA with dual-mode imaging characteristics are promising for targeted and image-guided siRNA therapy of hepatocellular carcinoma.
Keywords: autophagy; dual-mode imaging; hepatocellular carcinoma; small interfering RNA; theragnostic nanoparticles.
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