Enhanced delivery of sorafenib with anti-GPC3 antibody-conjugated TPGS-b-PCL/Pluronic P123 polymeric nanoparticles for targeted therapy of hepatocellular carcinoma

Materials Science & Engineering. C, Materials for Biological Applications
Huaiyong GanXiaolong Tang

Abstract

Although sorafenib (SFB) showed improved efficacy and much reduced the side effects in clinical liver cancer therapy, its therapeutic efficacy was still greatly limited due to short half-life in vivo as well as drug resistance. To solve these problems, we developed a novel SFB-loaded polymeric nanoparticle for targeted therapy of liver cancer. This polymeric nanoparticle, referred to NP-SFB-Ab, was fabricated from self-assembly of biodegradable block copolymers TPGS-b-poly(caprolactone) (TPGS-b-PCL) and Pluronic P123 and drug SFB, followed by conjugating the anti-GPC3 antibody. NP-SFB-Ab showed robust stability and achieve excellent SFB release in cell medium. The CLSM demonstrated that the Ab-conjugated NP exhibited much higher cellular uptake in HepG2 human liver cells than non-targeted NP. The MTT assay also confirmed that NP-SFB-Ab caused much greater cytotoxicity than non-targeted NP-SFB and free SFB. Finally, NP-SFB-Ab was proved to greatly inhibit the tumor growth of HepG2 xenograft-bearing nude mice without obvious side effects. Therefore, this NP-SFB-Ab provides a promising new approach for targeted therapy of hepatocellular carcinoma.

Citations

Feb 29, 2020·Journal of Cancer Research and Clinical Oncology·Maonan WangXuemei Wang
Feb 20, 2021·Drug Design, Development and Therapy·Huajing YangWen Cheng
May 26, 2021·Biomaterials Science·Mohammed Mehadi Hassan ChowdhuryMd Nurunnabi
Jul 6, 2021·International Journal of Biological Macromolecules·Jamileh KadkhodaAyuob Aghanejad
Jul 17, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Mohamed Fawzi KabilIbrahim M El-Sherbiny

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