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.

Drug Delivery
|June 20, 2018
PubMed

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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