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

摘要

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.