Shi Leilei, Wu Wenbo, Duan Yukun, Xu Li, Li Sha, Gao Xihui, Liu Bin
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
Joint Research Center for Precision Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, 6600th Nanfeng Road, Shanghai 201499, China.
ACS Nano. 2021 Jan 26;15(1):1841-1849. doi: 10.1021/acsnano.0c10045. Epub 2021 Jan 15.
Herein, we developed hybrid DNAzyme nanoparticles (NPs) to achieve light-induced carrier-free self-delivery of DNAzymes with sufficient cofactor supply and lysosome escape capacity. In this system, aggregation-induced emission (AIE) photosensitizer (PS) (TBD-Br) was grafted onto a phosphorothiolated DNAzyme backbone, which automatically self-assembled to form NPs and the surface phosphorothioate group could easily coordinate with the cofactor Zn in the buffer. When the yielded hybrid DNAzyme NPs were located inside tumor cell lysosomes, the O from TBD-Br under light illumination could destroy lysosome structure and promote the Zn coordinated DNAzyme NPs escape. Both in vitro and in vivo results demonstrated that the hybrid DNAzyme NPs could downregulate the early growth response factor-1 protein (EGR-1) to inhibit tumor cell growth in addition to induce tumor cell apoptosis by AIE PS (TBD-Br) under light irradiation.
在此，我们开发了混合脱氧核酶纳米颗粒（NPs），以实现光诱导的脱氧核酶无载体自递送，并具备充足的辅因子供应和溶酶体逃逸能力。在该系统中，聚集诱导发光（AIE）光敏剂（PS）（TBD-Br）被接枝到硫代磷酸化脱氧核酶主链上，其自动自组装形成纳米颗粒，且表面硫代磷酸基团可轻松与缓冲液中的辅因子锌配位。当产生的混合脱氧核酶纳米颗粒位于肿瘤细胞溶酶体内时，光照下TBD-Br中的氧可破坏溶酶体结构，促进锌配位的脱氧核酶纳米颗粒逃逸。体外和体内结果均表明，混合脱氧核酶纳米颗粒除了在光照下通过AIE PS（TBD-Br）诱导肿瘤细胞凋亡外，还可下调早期生长反应因子-1蛋白（EGR-1）以抑制肿瘤细胞生长。
