Hepatoma-targeting and reactive oxygen species-responsive chitosan-based polymeric micelles for delivery of celastrol

A glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) conjugate was designed and synthesized for the in vivo delivery of celastrol (Cela). Cela was encapsulated into polymeric micelles (PMs) formed by GCTR conjugates self-assembly in water to form Cela/GCTR PMs with high drug loading capacity and small particle size. Cela/GCTR PMs had a sustained-release characteristic in the blood environment and a rapid-release feature in the tumor microenvironment. Cela/GCTR PMs had a significant proliferation inhibitory effect on HepG2 and BEL-7402 cells, but a negligible impact on L-02 cells at low concentrations. Cela/GCTR PMs possessed reactive oxygen species (ROS)-responsive properties in vitro and in cells, could improve the bioavailability of Cela, and exert remarkable hepatoma-targeting properties. Cela/GCTR PMs could also effec-tively inhibit tumor growth with no apparent damage to different organs. In summary, GCTR PMs with good ROS-responsive and hepatoma-targeting properties are expected to be possible delivery carriers for hydrophobic antineoplastic drugs for hepatocellular carcinoma therapy.

Automated summary

A glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) conjugate was synthesized for the in vivo delivery of celastrol. Celastrol was encapsulated into polymeric micelles formed by GCTR conjugates self-assembly in water, resulting in celastrol/GCTR PMs with high drug loading capacity and small particle size. Celastrol/GCTR PMs exhibited sustained-release in the blood environment and rapid-release in the tumor microenvironment, showing significant proliferation inhibitory effect on HepG2 and BEL-7402 cells and negligible impact on L-02 cells at low concentrations. The reactive oxygen species (ROS)-responsive properties of celastrol/GCTR PMs improved the bioavailability of celastrol and showed remarkable hepatoma-targeting properties. Celastrol/GCTR PMs effectively inhibited tumor growth with no apparent damage to different organs.