Multi-Targeted Peptide-Modified Gold Nanoclusters for Treating Solid Tumors in the Liver

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Apoptosis and autophagy are crucial in cancer cell fate, but targeting apoptosis alone is insufficient for unresectable solid liver tumors.
• Autophagy typically acts as an anti-apoptotic mechanism, yet excessive endoplasmic reticulum (ER) stress can trigger its pro-apoptotic effects.

Purpose of the Study:

• To design and evaluate amphiphilic peptide-modified gold nanocluster aggregates (AP1P2-PEG NCs) for enhanced liver tumor treatment.
• To investigate the synergistic promotion of autophagy and apoptosis in liver tumor cells via ER stress induction.

Main Methods:

• Development of AP1P2-PEG NCs designed for liver tumor enrichment and prolonged ER stress.
• Evaluation of anti-tumor effectiveness in orthotopic and subcutaneous liver tumor models.
• Assessment of biosafety, therapeutic window, and stability (e.g., blood half-life).

Main Results:

• AP1P2-PEG NCs exhibited significant anti-tumor effectiveness in liver tumor models, outperforming sorafenib.
• The nanoclusters demonstrated excellent biosafety (LD50 of 827.3 mg/kg), a wide therapeutic window, and high stability (4h blood half-life).
• The strategy achieved mutual promotion of autophagy and apoptosis in liver tumor cells.

Conclusions:

• Peptide-modified gold nanocluster aggregates offer a potent and selective strategy for solid liver tumor treatment.
• This approach leverages ER stress to activate pro-apoptotic autophagy, enhancing anti-tumor efficacy.
• The developed nanoclusters present a promising low-toxicity, high-potency therapeutic option for liver cancer.