Authors

Jingru Xu ^1 2, Mengjie Gu ^1 2, Lissa Hooi ², Tan Boon Toh ³, Dexter Kai Hao Thng ², Jhin Jieh Lim ², Edward Kai-Hua Chow ^{1 2 3 4 5 6}

Affiliations

¹Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore. csikce@nus.edu.sg.

²Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore.

³The N.1 Institute for Health, National University of Singapore, 117456, Singapore.

⁴Department of Biomedical Engineering, National University of Singapore, 117583, Singapore.

⁵NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University Singapore, Singapore.

⁶The Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore.

Abstract
Small interfering RNA (siRNA) can cause specific gene silencing and is considered promising for treating a variety of cancers, including hepatocellular carcinoma (HCC). However, siRNA has many undesirable physicochemical properties that limit its application. Additionally, conventional methods for delivering siRNA are limited in their ability to penetrate solid tumors. In this study, nanodiamonds (NDs) were evaluated as a nanoparticle drug delivery platform for improved siRNA delivery into tumor cells. Our results demonstrated that ND-siRNA complexes could effectively be formed through electrostatic interactions. The ND-siRNA complexes allowed for efficient cellular uptake and endosomal escape that protects siRNA from degradation. Moreover, ND delivery of siRNA was more effective at penetrating tumor spheroids compared to liposomal formulations. This enhanced penetration capacity makes NDs ideal vehicles to deliver siRNA against solid tumor masses as efficient gene knockdown and decreased tumor cell proliferation were observed in tumor spheroids. Evaluation of ND-siRNA complexes within the context of a 3D cancer disease model demonstrates the potential of NDs as a promising gene delivery platform against solid tumors, such as HCC.

PMID: 34542130

DOI: 10.1039/d1nr03502a