Chain-shattering Pt(IV)-backboned polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic cancer therapy
Chain-shattering Pt(IV)-backboned polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic cancer therapy
复制标题
用于高效 CRISPR/Cas9 基因编辑的链断裂 Pt(IV) 骨架聚合物纳米平台，以增强协同癌症治疗
DOI：
10.1007/s12274-020-3066-4
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发表时间：
2020-10
期刊：
影响因子：
9.9
通讯作者：
Huang Yubin
中科院分区：
文献类型：
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作者：
Zhang Qingfei;Kuang Gaizhen;He Shasha;Liu Sha;Lu Hongtong;Li Xiaoyuan;Zhou Dongfang;Huang Yubin
CRISPR/Cas9系统已经成为一种很有前途的癌症治疗基因编辑工具。然而，开发一种简单有效的纳米载体，将CRISPR/Cas9系统与化疗药物结合起来，同时解决病毒载体的生物安全性和包装能力问题，并将基因编辑-化疗结合起来进行癌症治疗仍然是一个挑战。本文开发了一种链破碎Pt（IV）骨架聚合物纳米平台，用于递送ezh2靶向CRISPR/Cas9系统（NPCSPt/pEZH2）并协同治疗前列腺癌。在癌细胞中，pEZH2/Pt（II）可以有效地触发NPCSPt/pEZH2以链破碎的方式解包/释放。EZH2基因在体外对PC-3细胞的破坏效率可达32.2%，在体内对肿瘤组织的破坏效率可达21.3%，从而有效抑制EZH2蛋白的表达。此外，EZH2抑制后，H3K27me3显著下调，导致染色质结构更加宽松，从而增加释放的Pt（II）对核DNA的可及性，从而促进细胞凋亡。综上所述，可以实现对前列腺癌细胞的大量增殖抑制和对皮下异种移植肿瘤的85.4%的生长抑制。这种破链Pt（IV）骨架聚合物纳米平台系统不仅为CRISPR/Cas9系统递送提供了一种有前景的纳米载体，而且拓宽了基因编辑-化疗协同癌症治疗的潜力。
CRISPR/Cas9 system has become a promising gene editing tool for cancer treatment. However, development of a simple and effective nanocarrier to incorporate CRISPR/Cas9 system and chemotherapeutic drugs to concurrently tackle the biological safety and packaging capacity of viral vectors and combine gene editing-chemo for cancer therapy still remains challenges. Herein, a chain-shattering Pt(IV)-backboned polymeric nanoplatform is developed for the delivery of EZH2-targeted CRISPR/Cas9 system (NPCSPt/pEZH2) and synergistic treatment of prostate cancer. The pEZH2/Pt(II) could be effectively triggered to unpack/release from NPCSPt/pEZH2 in a chain-shattering manner in cancer cells. The EZH2 gene disruption efficiency could be achieved up to 32.2% of PC-3 cells in vitro and 21.3% of tumor tissues in vivo, leading to effective suppression of EZH2 protein expression. Moreover, significant H3K27me3 downregulation could occur after EZH2 suppression, resulting in a more permissive chromatin structure that increases the accessibility of released Pt(II) to nuclear DNA for enhanced apoptosis. Taken together, substantial proliferation inhibition of prostate cancer cells and further 85.4% growth repression against subcutaneous xenograft tumor could be achieved. This chain-shattering Pt(IV)-backboned polymeric nanoplatform system not only provides a prospective nanocarrier for CRISPR/Cas9 system delivery, but also broadens the potential of combining gene editing-chemo synergistic cancer therapy.
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影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
用于癌症治疗的基因组编辑：通过金纳米簇/脂质核壳纳米载体递送 Cas9 蛋白/sgRNA 质粒
影响因子：
15.1
作者：
Wang, Peng;Zhang, Lingmin;Jiang, Xingyu
通讯作者：
Jiang, Xingyu
DOI：
10.1016/j.respe.2020.09.004
发表时间：
2020-10-10
期刊：
Revue D'Epidemiologie et De Sante Publique
影响因子：
--
作者：
La rédaction
通讯作者：
La rédaction
影响因子：
9.3
作者：
通讯作者：
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