Intraorgan Targeting of Gold Conjugates for Precise Liver Cancer Treatment

Area of Science:

• Nanomedicine
• Oncology
• Bioconjugate Chemistry

Background:

• Targeting drug delivery to tumor tissues is crucial for treating solid tumors, especially when target receptors are present in both cancerous and normal tissues.
• Developing strategies for intraorgan targeting can enhance therapeutic efficacy and minimize off-target toxicity in liver cancer treatment.

Purpose of the Study:

• To fabricate asialoglycoprotein receptor (ASGP-R)-targeting paclitaxel-conjugated gold nanoparticles (Gal/PTX-GNPs) for precise liver cancer treatment.
• To evaluate the enhanced biological specificity and therapeutic performance of these targeted nanoparticles.

Main Methods:

• Synthesis of paclitaxel-conjugated gold nanoparticles with galactose modification for ASGP-R targeting.
• Assessment of tumor cell selectivity using liver cancer (HepG2) and normal liver (L02) cells.
• Quantification of drug distribution in tumor versus liver tissue at 8 hours post-injection in vivo.
• Evaluation of therapeutic performance in heterotopic and orthotopic Heps xenograft tumor models.

Main Results:

• The designed Gal/PTX-GNPs demonstrated approximately six times higher selectivity for liver tumor cells compared to control nanoparticles in normal liver cells.
• A 15.7-fold increase in tumor specificity was observed, with a drug level ratio of 121.0% in tumor versus liver at 8 hours post-injection.
• Significant improvements in therapeutic performance were noted in both heterotopic and orthotopic Heps xenograft models.

Conclusions:

• The intraorgan-targeting strategy using ASGP-R-targeting paclitaxel-conjugated gold nanoparticles offers enhanced antitumor efficacy for liver cancer.
• This approach significantly reduces hepatotoxicity, presenting a promising therapeutic option for liver cancer treatment.