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Updated: Feb 8, 2026

A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma
Xiaolong Tang1, Longzhou Chen2, Amin Li1
1a Medical College , Anhui University of Science and Technology , Huainan , China.
Abstract:
Sorafenib (SFB) has improved the treatment of hepatocellular carcinoma (HCC) and has fewer severe side effects than other agents used for that purpose. However, due to a lack of tumor-specific targeting, the concentration of the drug in tumor tissue cannot be permanently maintained at a level that inhibits tumor growth. To overcome this problem, we developed a novel SFB-loaded polymer nanoparticle (NP). The NP (a TPGS-b-PCL copolymer that was synthesized from ε-caprolactone and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via ring-opening polymerization) contains Pluronic P123 and SFB, and its surface is modified with anti-GPC3 antibody to produce the polymer nanoparticle (NP-SFB-Ab). The Ab-conjugated NPs had higher cellular uptake by HepG2 cells than did non-antibody-conjugated SPD-containing nanoparticles (NP-SFB). The NP-SFB-Ab also displayed better stability characteristics, released higher levels of SFB into cell culture medium, and was more cytotoxic to tumor cells than was non-targeted NP-SFB and free SFB. The NP-SFB-Ab downregulated expression of the anti-apoptosis molecule MCL-1, which led to polymerization of Bax and Bak in mitochondrial cytosol. The NP-SFB-AB also promoted the mitochondrial release of cytochrome C, resulting in cellular apoptosis. Moreover, the NP-SFB-Ab significantly inhibited the growth of HepG2 xenograft tumors in nude mice without producing obvious side effects. These findings suggest that NP-SFB-Ab is a promising new method for achieving targeted therapy of HCC.
Insights
This study developed targeted nanoparticles loaded with sorafenib (SFB) to treat liver cancer (HCC). These novel nanoparticles show improved drug delivery, enhanced tumor cell killing, and reduced side effects, offering a promising new therapy.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Sorafenib (SFB) is a key treatment for hepatocellular carcinoma (HCC), but its efficacy is limited by poor tumor targeting.
- Achieving sustained therapeutic drug concentrations within tumors remains a challenge for current HCC treatments.
Purpose of the Study:
- To develop a novel, targeted nanoparticle system for improved delivery of sorafenib (SFB) in hepatocellular carcinoma (HCC) treatment.
- To enhance the anti-cancer efficacy and reduce systemic toxicity of SFB through targeted delivery.
Main Methods:
- Synthesized SFB-loaded polymer nanoparticles (NPs) using TPGS-b-PCL copolymer, incorporating Pluronic P123 and SFB.
- Conjugated anti-GPC3 antibodies to the NP surface (NP-SFB-Ab) for targeted delivery to HCC cells.
- Evaluated cellular uptake, stability, drug release, cytotoxicity, apoptosis induction, and in vivo tumor growth inhibition in HCC models.
Main Results:
- NP-SFB-Ab demonstrated significantly higher cellular uptake in HepG2 cells compared to non-targeted NPs (NP-SFB).
- NP-SFB-Ab exhibited enhanced stability, increased SFB release, and superior cytotoxicity against tumor cells.
- The targeted NPs induced apoptosis by downregulating MCL-1 and promoting cytochrome C release, significantly inhibiting tumor growth in vivo with minimal side effects.
Conclusions:
- The novel antibody-conjugated nanoparticle system (NP-SFB-Ab) effectively targets and delivers SFB to HCC cells, enhancing therapeutic outcomes.
- This targeted nanoparticle approach represents a promising strategy for improving the efficacy and safety of HCC treatment.
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