Functionalized MoS₂ Nanosheets as Multi-Gene Delivery Vehicles for <i>In Vivo</i> Pancreatic Cancer Therapy

Abstract

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, <i>in vitro</i> cell growth rate, and <i>in vivo</i> 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 <i>in vitro</i> and <i>in vivo</i> 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 <i>in vivo</i> pancreatic adenocarcinoma therapy.