Molybdenum disulfide/graphene oxide nanocomposites show favorable lung targeting and enhanced drug loading/tumor-killing efficacy with improved biocompatibility

Abstract

Selective targeting plus optimal biocompatibility is still a big challenge in nanomedicine. Although many nanomaterials including graphene oxide (GO) and molybdenum disulfide (MoS2) have been tested for this purpose, these materials possess both favorable features and drawbacks, which hampers their further development. Herein, we prepared MoS2/GO nanocomposites that manifested excellent dispersity in aqueous solutions and revealed acceptable biocompatibility in vitro and in vivo. Importantly, MoS2/GO displayed a novel feature to selectively target the lung. In other words, MoS2/GO manifested a pronounced tendency of localization towards the lung comparable to GO, offering a ‘guided missile’ effect in targeting the lung. Furthermore, MoS2/GO composites possessed enhanced drug loading capacity together with reinforced tumor-killing efficacy against cancer cells that have the propensity to metastasize to the lung. Importantly, MoS2/GO composites remarkably repressed metastatic tumor growth of B16 murine melanoma cancer cells in lungs of mice. Mechanistically, MoS2/GO was demonstrated to reveal compromised reactions towards macrophages at the nano-bio interface relative to GO, which is accountable for the interaction and the uptake of nanosheets by macrophages associated with phagocytosis and macrophagic activation. Considered together, our findings established new MoS2/GO nanocomposites with multi-functionalities including selective lung targeting, favorable drug loading capacity, elevated tumor killing efficacy and improved biocompatibility. Our study opens an avenue for MoS2/GO nanocomposites in cancer nanotheranostics. Graphene oxide nanosheets decorated with molybdenum and drug agents show promising action against lung metastatic cancer cells in live mice. Unlike other nanomaterials, graphene-based compounds can appear in the lungs after being captured by capillary cells. This accumulation sometimes produces toxic side-effects, but a team led by Sijin Liu from the Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, reports better biocompatibility with graphene oxide-molybdenum disulfide composites. Interlayering of the two sheet-like components produced a substance well suited for aqueous environments and with strong affinity for chemotherapeutic agents such as doxorubicin. Experiments revealed that drug-loaded nanocomposites exhibited preferential targeting of the lungs and substantially inhibited metastatic tumor growth in the lungs of mice. Biosafety improvements were attributed to a reduction in macrophage interactions due to the nanosheets' lack of active oxygen-based surface species. Herein, an idea of creating MoS2/GO nanocomposites was brought about, which were constructed to integrate the merits for both materials with additional benefits and shield the mutual weaknesses. It turned out that MoS2/GO nanocomposites manifested beneficial multi-functionalities including favorable lung targeting, enhanced drug loading capacity, increased tumor killing efficacy and improved biosafety as well. This study would open a new path that may lead to desirable use of MoS2/GO nanocomposites in cancer therapeutics.