Dual-Function, Cationic, Peptide-Coated Nanodiamond Systems : Facilitating Nuclear-Targeting Delivery for Enhanced Gene Therapy Applications

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

26 Scopus Citations
View graph of relations

Detail(s)

Original languageEnglish
Pages (from-to)9671-9681
Journal / PublicationACS Sustainable Chemistry and Engineering
Volume6
Issue number8
Online published6 Jul 2018
Publication statusPublished - 6 Aug 2018

Abstract

Nuclear-targeting therapy is considered to be a promising strategy of disease treatment. So far, developing biocompatible and nucleus-permeable delivery systems remains a great challenge. Here, we report a nuclear-targeted delivery platform based on 30 nm nanodiamonds (NDs) which were coated with dual-function, cationic peptides consisting of the human immounodeficiency virus TAT protein and a nuclear localization signal (NLS) peptide in aqueous media. As compared to uncoated NDs, cationic peptide-functionalized NDs were confirmed as a small, safe, and efficient carrier which not only facilitates the enhanced cellular uptake and delivery of loaded cargos to the nucleus in a number of cell lines but also shows their advantages of low cytotoxicity and high affinity to antisense oligonucleotides. This peptide-based modification strategy does not contribute greatly to the size of the ND which is important in its use in constructing nuclear targeting vehicles. Compared with traditional gene silencing in cytoplasm, our findings suggest that the nuclear localization effect of ANA4625-TAT-NLS-NDs enhances the therapeutic efficacy of antisense oligonucleotide ANA4625 as evidenced by suppression of the targets bcl-2 and bcl-xL pre-mRNA/protein expressions and the induction of cell apoptosis. The studies have also revealed that NDs can be used to mediate sustained release of antisense agents with preserved therapeutic activity as inhibition of target mRNA expression in a time- and dose-dependent manner. This work not only demonstrates the design of a new nanodiamond-based platform for nuclear targeting but also provides significant insights on nuclear-targeting delivery of cell membrane impermeable therapeutic agents for enhanced disease treatment.

Research Area(s)

  • Nanodiamond, Nucleus targeting, Antisense oligonucleotide, Delivery, Protein expression

Citation Format(s)

Dual-Function, Cationic, Peptide-Coated Nanodiamond Systems : Facilitating Nuclear-Targeting Delivery for Enhanced Gene Therapy Applications. / Leung, Hoi Man; Chan, Miu Shan; Liu, Ling Sum; Wong, Sze Wing; Lo, Tsz Wan; Lau, Cia-Hin; Tin, Chung; Lo, Pik Kwan.

In: ACS Sustainable Chemistry and Engineering, Vol. 6, No. 8, 06.08.2018, p. 9671-9681.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review