1 research outputs found
Dual-Function, Cationic, Peptide-Coated Nanodiamond Systems: Facilitating Nuclear-Targeting Delivery for Enhanced Gene Therapy Applications
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 <i>bcl-2</i> and <i>bcl-xL</i> 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