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Nanotheranostics 2018; 2(4):371-386. doi:10.7150/ntno.27308 This issue Cite

Research Paper

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

Feng Yin^1,2#, Tommy Anderson^2#, Nishtha Panwar^2#, Kang Zhang², Swee Chuan Tjin², Beng Koon Ng², Ho Sup Yoon³, Junle Qu⁴, Ken-Tye Yong ^2✉

1. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China
2. School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore
3. Division of Structural Biology & Biochemistry, School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore
4. Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, People's Republic of China
^# Equal contribution

✉ Corresponding author: ktyongedu.sg

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, 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.

Keywords: MoS₂, HDAC1, KRAS, gene delivery, pancreatic cancer cells

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