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Aggregation-Induced Emission (AIE) and Magnetic Resonance Imaging Characteristics for Targeted and Image-Guided siRNA
Yu-Chen Hou1,2,3, Chao Zhang3,4, Zi-Jie Zhang1,2,3
1Shanghai Institute of Transplantation, Shanghai, 200127, China.
Abstract:
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.
Insights
This study introduces novel nanoparticles for targeted hepatocellular carcinoma (HCC) therapy. These dual-mode imaging nanoparticles effectively deliver Survivin siRNA, suppressing tumor growth with reduced toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent global cancer.
- Small interfering RNA (siRNA) offers gene silencing therapy but faces challenges like off-target effects and in vivo quantification.
- Effective targeted therapies with imaging capabilities are needed for HCC treatment.
Purpose of the Study:
- To develop a novel theragnostic nanoparticle for targeted and image-guided siRNA therapy of HCC.
- To evaluate the nanoparticle's dual-mode imaging (MRI and AIE) and therapeutic efficacy in HCC.
Main Methods:
- Synthesized theragnostic nanoparticles (T7-AIE/Gd NPs) encapsulating Survivin siRNA using Poly-ethylenimine (PEI).
- Nanoparticles self-assembled from DSPE-PEG-DTPA(Gd), DSPE-PEG-Mal, DSPE-PEG-PEI, and TPE.
- Evaluated in vitro toxicity and therapeutic effects, and in vivo dual-mode imaging (MRI and AIE) and tumor suppression in HCC models.
Main Results:
- The theragnostic nanoparticles demonstrated low toxicity and high therapeutic efficacy.
- Achieved excellent T1-weighted magnetic resonance imaging (MRI) and aggregation-induced emission (AIE) imaging performance.
- In vivo imaging confirmed rapid tumor accumulation via active targeting and EPR effects, leading to suppressed HCC growth through autophagy induction and DNA destabilization.
Conclusions:
- T7-AIE-Gd nanoparticles carrying Survivin siRNA show promise for targeted HCC therapy.
- Dual-mode imaging provides effective monitoring of nanoparticle delivery and therapeutic response.
- This theragnostic approach offers a potential strategy for image-guided HCC treatment.
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