A Nucleic Acid/Gold Nanorod-Based Nanoplatform for Targeted Gene Editing and Combined Tumor Therapy
2021
Tang, Wantao | Han, Lin | Lu, Xuehe | Wang, Zhaoran | Liu, Fengsong | Li, Yan | Liu, Shengbo | Liu, Shaoli | Tian, Run | Liu, Jianbing | Ding, Baoquan
The CRISPR/Cas9 gene-editing system has become a promising strategy for tumor therapy with its powerful oncogene-editing ability. However, the efficient delivery of sgRNA/Cas9 complex into target tumor cells remains a challenge. Herein, we report a facile strategy for the construction of an sgRNA/Cas9 complex co-assembled nanoplatform for targeted gene editing and combined tumor therapy. In our design, the TAT peptide and thiolated DNA linker functionalized gold nanorod can efficiently load the sgRNA/Cas9 complex through the hybridization between the 3′ overhang of sgRNA and the DNA linker. Due to the integration of an active cell targeting group (aptamer) and nuclear targeting peptide (TAT), the multifunctional nanoplatform can elicit the targeted cellular internalization and efficient nuclear targeting transportation to realize endogenous RNase H activated gene editing of the tumor-associated gene polo-like kinase 1 (PLK1). With mild photothermal treatment, this sgRNA/Cas9 complex loaded nanoplatform achieved efficient inhibition of tumor cell proliferation. This multifunctional nanocarrier provides a new strategy for the development of combined tumor therapy.
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