Expansile Nanoparticles Encapsulate Factor Quinolinone Inhibitor 1 and Accumulate in Murine Liver upon Intravenous Administration

Abstract

Expansile nanoparticles (eNPs) are a promising pH-responsive polymeric drug delivery vehicle, as demonstrated in multiple intraperitoneal cancer models. However, previous delivery routes were limited to intraperitoneal injection and to a single agent, paclitaxel. In this study, we preliminarily evaluate the biodistribution and in vivo toxicity of eNPs in mice after intravenous injection. The eNPs localize predominantly to the liver, without detectable acute toxicity in the liver or other key organs. On the basis of these results, we encapsulated FQI1, a promising lead compound for treatment of hepatocellular carcinoma, in eNPs. eNPs are taken up by cancerous and noncancerous human liver cells in vitro, although at different rates. FQI1-loaded eNPs release FQI1 in a pH-dependent manner and limit proliferation equivalently to unencapsulated FQI1 in immortalized hepatocytes in vitro. eNPs are a versatile platform delivery system for therapeutic compounds and have potential utility in the treatment of liver disease.

The Emerging Roles of Silver Nanoparticles to Target Viral Life Cycle and Detect Viral Pathogens

“…Hepatitis C virus is an enveloped, positive, single stranded RNA virus that causes chronic infections in liver, including cirrhosis, liver failure and hepatocellular carcinoma. [93] The HCV RNA genomes encodes a polyprotein that is cleaved by cellular and viral proteases to generate structural proteins that assist in viral capsid and envelop formations as well as nonstructural proteins that guide replication, modulation of host defense mechanisms, assembly and maturation. [94] NS3 is a non-structural serine protease that consists of a N-terminal protease domain that coordinates viral gene expression and a C-terminal helicase domain that facilitates viral gene replication.…”