Tumor-Targeted\nCO Nanodelivery System Design and Therapy\nfor Hepatocellular Carcinoma

In\nrecent years, carbon monoxide (CO) has garnered increased\nattention\nas a novel green therapy for hepatocellular carcinoma (HCC) treatment.\nHowever, the CO donor is still limited in clinical application due\nto its lack of targeted ability and unstable release rate. Here, self-assembled\namphiphilic nanomicelles glucose-polyethylene glycol (PEG)–lipoic\nacid (LA)–Fe<sub>2</sub>(CO)<sub>6</sub> (Glu-Fe<sub>2</sub>(CO)<sub>6</sub>) are first designed as a CO donor and synthesized\nvia a chemical method, combining glucose with Fe<sub>2</sub>(CO)<sub>6</sub> through PEG–LA. Some advantages of this tumor-targeted\nGlu-Fe<sub>2</sub>(CO)<sub>6</sub> delivery system include (I) good\nwater-solubility, (II) the glutathione responsive CO slow release,\n(III) the active tumor-targeted ability of glucose as targeted ligands,\nand (IV) outstanding efficacy of antitumor and safety of CO therapy\nof HCC both in vitro and in vivo. These findings suggest that Glu-Fe<sub>2</sub>(CO)<sub>6</sub> nanomicelles hold promise for enhancing antitumor\ntherapeutic capabilities, presenting a novel tumor-targeted delivery\nstrategy in gas therapy for HCC treatment.