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Ultrasound and ROS-responsive nanodroplets inhibit TCA cycle in hepatocellular carcinoma
Ting Zhao1, Lu Guo1, Ning Cong1
1Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Journal of Nanobiotechnology
|March 1, 2026
Summary
This study introduces a novel nanodroplet therapy for liver cancer (HCC). The treatment targets cancer cell metabolism, achieving up to 95.1% tumor inhibition by blocking key energy pathways.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Hepatocellular carcinoma (HCC) cells exhibit altered energy metabolism, notably upregulating the tricarboxylic acid (TCA) cycle.
- Metabolic reprogramming is a hallmark of cancer, providing cancer cells with energy for proliferation.
Purpose of the Study:
- To develop a targeted therapeutic strategy for HCC by exploiting its metabolic vulnerabilities.
- To investigate the synergistic effects of a novel nanodroplet system and ultrasound-triggered drug release on HCC growth.
Main Methods:
- Construction of novel ROS- and ultrasound-responsive nanodroplets (sGTNDs) loaded with G6PD siRNA and modified with GA.
- Targeted delivery of sGTNDs to HCC via GA receptor recognition.
- Ultrasound-targeted microbubble destruction (UTMD) to trigger sGTND payload release (GA and G6PD siRNA).
Main Results:
- sGTNDs demonstrated excellent biocompatibility and contrast-enhanced ultrasound imaging capabilities.
- Targeted delivery and release of GA activated NRF2, while siRNA inhibited G6PD.
- The combined therapy synergistically inhibited the TCA cycle, leading to a significant antitumor efficacy of 95.1% in HCC models.
Conclusions:
- The combination of sGTND and UTMD offers a promising dual-action therapeutic approach for HCC.
- This strategy effectively inhibits the TCA cycle by activating NRF2 and inhibiting G6PD, showcasing significant antitumor potential.
