@article{Zhang2021, author = {Qingfei Zhang and Gaizhen Kuang and Shasha He and Sha Liu and Hongtong Lu and Xiaoyuan Li and Dongfang Zhou and Yubin Huang}, title = {Chain-shattering Pt(IV)-backboned polymeric nanoplatform for efficient CRISPR/Cas9 gene editing to enhance synergistic cancer therapy}, year = {2021}, journal = {Nano Research}, volume = {14}, number = {3}, pages = {601-610}, keywords = {gene editing, combination therapy, CRISPR/Cas9, EZH2, Pt(IV)-backboned polymeric nanoplatform}, url = {https://www.sciopen.com/article/10.1007/s12274-020-3066-4}, doi = {10.1007/s12274-020-3066-4}, abstract = {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.} }