Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery
Menghan Wang1, Xing Ma1, Guoyu Wang1
1Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Rd, Pudong New Area, Shanghai, 200137, China.
Background:
Hepatocellular carcinoma (HCC) is among the most common and malignant cancers with no effective therapeutic approaches. Echinacoside (ECH), a phenylethanoid glycoside isolated from Chinese herbal medicine, Cistanche salsa, can inhibit HCC progression; however, poor absorption and low bioavailability limit its biological applications.
Methods:
To improve ECH sensitivity to HepG2 cells, we developed a mesoporous silica nanoparticle (MSN)-based drug delivery system to deliver ECH to HepG2 cells via galactose (GAL) and poly(ethylene glycol) diglycidyl ether (PEGDE) conjugation (ECH@Au@MSN-PEGDE-GAL, or ECH@AMPG). Gain- and loss-of-function assays were conducted to assess the effects of UBR5 on HCC cell apoptosis and glycolysis. Moreover, the interactions among intermediate products were also investigated to elucidate the mechanisms by which UBR5 functions.
Results:
The present study showed that ubiquitin protein ligase E3 component N-recognin 5 (UBR5) acted as an oncogene in HCC tissues and that its expression was inhibited by ECH. AMPG showed a high drug loading property and a slow and sustained release pattern over time. Moreover, owing to the valid drug accumulation, ECH@AMPG promoted apoptosis and inhibited glycolysis of HepG2 cells in vitro. In vivo experiments demonstrated that AMPG also enhanced the antitumor effects of ECH in HepG2 cell-bearing mice.
Conclusions:
Our results indicated the clinical significance of UBR5 as a therapeutic target. On the basis of the nontoxic and high drug-loading capabilities of AMPG, ECH@AMPG presented better effects on HCC cells compared with free ECH, indicating its potential for the chemotherapy of HCC.
Insights
This study developed a novel nanoparticle drug delivery system (ECH@AMPG) to enhance echinacoside (ECH) efficacy against hepatocellular carcinoma (HCC). The system effectively targets cancer cells, inhibits tumor growth, and shows potential for HCC chemotherapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer with limited therapeutic options.
- Echinacoside (ECH), a natural compound, shows promise against HCC but suffers from poor bioavailability.
- A mesoporous silica nanoparticle (MSN)-based system was developed to improve ECH delivery.
Purpose of the Study:
- To develop a drug delivery system enhancing ECH's anti-HCC effects.
- To investigate the role of ubiquitin protein ligase E3 component N-recognin 5 (UBR5) in HCC.
- To evaluate the efficacy of ECH delivered via the novel nanoparticle system.
Main Methods:
- Conjugation of galactose (GAL) and poly(ethylene glycol) diglycidyl ether (PEGDE) to MSN for ECH delivery (ECH@AMPG).
- In vitro assays including gain- and loss-of-function studies on UBR5 in HepG2 cells.
- In vitro and in vivo experiments to assess ECH@AMPG's anti-tumor activity and mechanism.
Main Results:
- ECH@AMPG demonstrated high drug loading and sustained release of ECH.
- The nanoparticle system promoted HepG2 cell apoptosis and inhibited glycolysis.
- UBR5 was identified as an oncogene in HCC, inhibited by ECH, and ECH@AMPG showed enhanced in vivo anti-tumor effects.
Conclusions:
- UBR5 is a potential therapeutic target for HCC.
- The developed ECH@AMPG system is nontoxic, exhibits high drug loading, and improves ECH's efficacy against HCC.
- ECH@AMPG holds promise as a potential therapeutic strategy for HCC chemotherapy.
