Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core–Shell Nanocarrier

The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)‐Cas9 (CRISPR‐associated protein) system (CRISPR‐Cas9) is a powerful toolbox for gene‐editing, however, the nonviral delivery of CRISPR‐Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV‐1‐transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei. This strategy is utilized to treat melanoma by designing sgRNA targeting Polo‐like kinase‐1 (Plk1) of the tumor. The nanoparticle (polyethylene glycol‐lipid/GNs/Cas9 protein/sgPlk1 plasmid, LGCP) leads to >70% down‐regulation of Plk1 protein expression of A375 cells in vitro. Moreover, the LGCP suppresses melanoma progress by 75% on mice. Thus, this strategy can deliver protein‐nucleic acid hybrid agents for gene therapy.