School of Materials Science and Engineering, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China.
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
ACS Appl Mater Interfaces. 2021 May 12;13(18):20974-20981. doi: 10.1021/acsami.1c02122. Epub 2021 Apr 28.
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.
CRISPR/Cas9 基因编辑系统凭借其强大的致癌基因编辑能力，已成为肿瘤治疗的一种有前途的策略。然而，将 sgRNA/Cas9 复合物有效递送至靶肿瘤细胞仍然是一个挑战。在此，我们报告了一种用于构建 sgRNA/Cas9 复合物共组装纳米平台的简便策略，用于靶向基因编辑和联合肿瘤治疗。在我们的设计中，TAT 肽和巯基化 DNA 接头功能化的金纳米棒可以通过 sgRNA 的 3'突出端与 DNA 接头之间的杂交，有效地负载 sgRNA/Cas9 复合物。由于整合了活性细胞靶向基团（适体）和核靶向肽（TAT），多功能纳米平台可以引发靶向细胞内吞作用和有效的核靶向运输，以实现肿瘤相关基因 polo 样激酶 1（PLK1）的内源性 RNase H 激活基因编辑。通过温和的光热治疗，这种负载 sgRNA/Cas9 复合物的纳米平台实现了对肿瘤细胞增殖的有效抑制。这种多功能纳米载体为联合肿瘤治疗的发展提供了一种新策略。
