EBNA1 Targeted Ultra-Small Near-Infrared Persistent Luminescent Nano-Inhibitor for Theranostics of EBV-Associated...

Area of Science:

• Oncology
• Nanotechnology
• Virology

Background:

• Epstein-Barr virus (EBV) is a known oncogenic virus implicated in various cancers.
• Epstein-Barr nuclear antigen 1 (EBNA1) is crucial for EBV replication and maintenance, making it a therapeutic target.
• Existing EBNA1 inhibitors face challenges with bioavailability and in vivo monitoring.

Purpose of the Study:

• To develop a novel nano-inhibitor for targeting EBNA1 in EBV-positive cancers.
• To evaluate the efficacy and targeting capabilities of the nano-inhibitor in vitro and in vivo.
• To explore the potential of near-infrared persistent luminescence (NIR-PL) imaging for monitoring treatment.

Main Methods:

• Fabrication of EBNA1-specific peptide (P4) functionalized ZnGa2O4:Cr3+ ultra-small NIR-PL nanoparticles (ZGOC-P4).
• Assessment of ZGOC-P4's selective inhibition of EBV-positive (C666-1) and EBV-negative (HK-1) nasopharyngeal carcinoma (NPC) cells.
• In vivo evaluation of ZGOC-P4 tumor targeting, accumulation, and therapeutic effect in an NPC xenograft model using NIR-PL imaging.

Main Results:

• ZGOC-P4 demonstrated rapid nuclear internalization and selective growth inhibition in EBV-positive NPC cells.
• No inhibitory effect was observed in EBV-negative NPC cells, confirming specificity.
• Efficient tumor-targeting accumulation was achieved in vivo, monitored by NIR-PL imaging.
• A significant tumor growth inhibition rate of 61.6% was achieved in the NPC xenograft model.

Conclusions:

• The developed ZGOC-P4 nano-inhibitor effectively targets and inhibits EBV-positive NPC growth.
• NIR-PL imaging provides a valuable tool for in vivo monitoring of the nano-inhibitor.
• This study offers a promising new strategy for treating EBV-associated malignancies.