Tumor-Targeted CO Nanodelivery System Design and Therapy for Hepatocellular Carcinoma

In recent years, carbon monoxide (CO) has garnered increased attention as a novel green therapy for hepatocellular carcinoma (HCC) treatment. However, the CO donor is still limited in clinical application due to its lack of targeted ability and unstable release rate. Here, self-assembled amphiphilic nanomicelles glucose-polyethylene glycol (PEG)-lipoic acid (LA)-Fe-2(CO)(6) (Glu-Fe-2(CO)(6)) are first designed as a CO donor and synthesized via a chemical method, combining glucose with Fe-2(CO)(6) through PEG-LA. Some advantages of this tumor-targeted Glu-Fe-2(CO)(6) delivery system include (I) good water-solubility, (II) the glutathione responsive CO slow release, (III) the active tumor-targeted ability of glucose as targeted ligands, and (IV) outstanding efficacy of antitumor and safety of CO therapy of HCC both in vitro and in vivo. These findings suggest that Glu-Fe-2(CO)(6) nanomicelles hold promise for enhancing antitumor therapeutic capabilities, presenting a novel tumor-targeted delivery strategy in gas therapy for HCC treatment.