CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China.
College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.
Angew Chem Int Ed Engl. 2022 Aug 22;61(34):e202206485. doi: 10.1002/anie.202206485. Epub 2022 Jul 13.
Despite the enormous potential of DNAzyme for gene therapy, its efficacy is hampered by the limited endosomal escape capability. Here, we develop a near-infrared (NIR) light-controlled DNAzyme delivery platform to achieve enhanced gene-silencing efficacy. The nanoplatform is composed of therapeutic DNAzyme, photosensitizers (PSs) and upconversion nanoparticles (UCNPs) that can convert NIR light to visible light. The system allows NIR light-activatable generation of cytotoxic reactive oxygen species due to the energy transfer from the UCNPs to PSs, which boosts the endosomal escape of DNAzyme for an improved gene-silencing efficacy. We demonstrate that the nanocomposites represent a promising platform to integrate DNAzyme-based gene therapy with NIR light-triggered photodynamic therapy for combinational tumor treatment. This work highlights a robust approach to combat the current limitations of DNAzyme delivery systems.
尽管 DNA zyme 在基因治疗方面具有巨大的潜力，但由于内体逃逸能力有限，其疗效受到限制。在这里，我们开发了一种近红外（NIR）光控 DNAzyme 递药平台，以实现增强的基因沉默疗效。该纳米平台由治疗性 DNAzyme、光敏剂（PSs）和上转换纳米粒子（UCNPs）组成，能够将 NIR 光转换为可见光。由于能量从 UCNPs 转移到 PSs，该系统允许 NIR 光激活产生细胞毒性活性氧物种，从而促进 DNAzyme 的内体逃逸，提高基因沉默疗效。我们证明，该纳米复合材料代表了一种有前途的平台，可以将基于 DNAzyme 的基因治疗与 NIR 光触发的光动力疗法相结合，用于联合肿瘤治疗。这项工作突出了一种强大的方法，可以克服 DNAzyme 递药系统当前的限制。
