Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, P. R. China.
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.
Small. 2022 Nov;18(47):e2204858. doi: 10.1002/smll.202204858. Epub 2022 Oct 10.
Programmable chiral biocatalysis represents a promising therapeutic strategy for its high stereospecific control over various biotransformations (e.g., chiral Aβ isomerization) of living entities yet is rarely explored. With an extraordinary resistance to nuclease digestion, the non-natural left-handed deoxyribozyme (l-DNAzyme) therapy is constrained by inefficient delivery/release and insufficient cofactors supply. Herein, an efficient adenosine triphosphate (ATP)-stimulated disassembly of l-histidine (l-His)-integrated ZIF-8 (l-His-ZIF-8) is reported for sustaining the l-DNAzyme-amplified photodynamic therapy. This self-sufficient l-therapeutic platform can intelligently release the l-DNAzyme probe and simultaneously supply l-His DNAzyme cofactors via endogenous ATP. Then, the intrinsic microRNA-21 catalyzes the generation of robust l-DNAzyme via the catalytic hybridization reaction for activating the photosensitizer with multiplied guaranteed therapeutic operation. This l-therapeutic strategy opens up great prospects for more precise diagnosis and customized gene silencing-based therapy.
可编程手性生物催化代表了一种很有前途的治疗策略，因为它可以高度立体专一地控制各种生物转化（例如，手性 Aβ 异构化），但很少被探索。非天然的左手脱氧核酶（l-DNAzyme）治疗具有非凡的抗核酸酶消化能力，但受到递送/释放效率低下和辅助因子供应不足的限制。本文报道了一种高效的三磷酸腺苷（ATP）刺激的整合 l-组氨酸（l-His）的 ZIF-8（l-His-ZIF-8）的解组装，以维持 l-DNAzyme 扩增的光动力治疗。这种自给自足的 l-治疗平台可以智能地释放 l-DNAzyme 探针，并通过内源性 ATP 同时提供 l-His DNAzyme 辅助因子。然后，内源性 microRNA-21 通过催化杂交反应生成强大的 l-DNAzyme，通过倍增保证治疗操作来激活光敏剂。这种 l-治疗策略为更精确的诊断和基于定制基因沉默的治疗开辟了广阔的前景。
