Functionalized MoS₂ Nanosheets as Multi-Gene Delivery Vehicles for In Vivo Pancreatic Cancer Therapy

Transition metal dichalcogenides (TMDCs) are categorized as novel two-dimensional (2D) nanomaterials with unique physical and chemical properties, bearing varied applications in medical and materials sciences. However, only a few works report the application of TMDCs for gene therapy in cancer treatment. Here, we engineer a multi-gene delivery system based on functionalized monolayer MoS₂, which can co-deliver HDAC1 and KRAS small interfering RNAs (siRNAs) to Panc-1 cancer cells for combinational cancer therapy. The synergistic effect of gene silencing therapy and NIR phototherapy is demonstrated by inhibition of both genes, in vitro cell growth rate, and in vivo tumor volume growth rate, exemplifying pre-eminent anticancer efficacy. This anti-tumor effect is a result of the photothermal effect of MoS₂ induced by NIR excitation and inactivation of HDAC1 and KRAS genes, which consequently bring about apoptosis, inhibit migration, and induce cell cycle arrest in the treated Panc-1 cells. Moreover, good biocompatibility and reduced cytotoxicity of MoS₂-based nanocarriers enable their metabolism within in vitro and in vivo mouse models over a prolonged duration without any evident ill-effects. In summary, we demonstrate the promising potential of low-toxicity, functionalized MoS₂ nanocarriers as a biocompatible gene delivery system for in vivo pancreatic adenocarcinoma therapy.