Serotonin-Stearic Acid Bioconjugate-Coated Completely Biodegradable Mn₃O₄ Nanocuboids for Hepatocellular Carcinoma Targeting

In this study, a serotonin-stearic acid (ST-SA)-based bioconjugate was synthesized for the surface modification of manganese oxide-based nanocuboids (MNCs) for delivering of anticancer drug (i.e., doxorubicin hydrochloride (DOX)) to human liver cancer cells. MNCs were synthesized by chemical precipitation method, and their surface was modified with ST-SA bioconjugate for targeting of MNCs to cancer cells. The ST-SA@MNCs along with DOX showed good colloidal stability, high drug encapsulation (98.3%), and drug loading efficiencies (22.9%) as well as pH-responsive biodegradation. Coating with ST-SA conjugate provided a shield to MNCs which sustained their degradation in an acidic environment. The release of DOX was higher (81.4%) in acidic media than under the physiological conditions (20.5%) up to 192 h. The in vitro anti-proliferation assay showed that ST-SA@MNCs exhibit higher cell growth inhibition compared to that of pure DOX after 48 h of treatment. The cellular uptake and apoptosis studies revealed the enhanced uptake of ST-SA@MNCs in contrast to the MNCs due to overexpressed ST receptor on hepatocellular carcinoma cells and triggered the generation of reactive oxygen species in the cells. Therefore, these results indicated that the DOX-loaded, ST-SA stabilized MNCs improved the therapeutic index of DOX and would be a promising therapeutic candidate for tumor therapy.