Abstract：
Emerging research suggests that mitochondrial DNA is a potential target for cancer treatment. However, achieving precise delivery of deoxyribozymes (DNAzymes) and combining photodynamic therapy (PDT) and DNAzyme-based gene silencing together for enhancing mitochondrial gene-photodynamic synergistic therapy remains challenging. Accordingly, herein, intelligent supramolecular nanomicelles are constructed by encapsulating a DNAzyme into a photodynamic O2 economizer for mitochondrial NO gas-enhanced synergistic gene-photodynamic therapy. The designed nanomicelles demonstrate sensitive acid- and red-light sequence-activated behaviors. After entering the cancer cells and targeting the mitochondria, these micelles will disintegrate and release the DNAzyme and Mn (II) porphyrin in the tumor microenvironment. Mn (II) porphyrin acts as a DNAzyme cofactor to activate the DNAzyme for the cleavage reaction. Subsequently, the NO-carrying donor is decomposed under red light irradiation to generate NO that inhibits cellular respiration, facilitating the conversion of more O2 into singlet oxygen (1 O2 ) in the tumor cells, thereby significantly enhancing the efficacy of PDT. In vitro and in vivo experiments reveal that the proposed system can efficiently target mitochondria and exhibits considerable antitumor effects with negligible systemic toxicity. Thus, this study provides a useful conditional platform for the precise delivery of DNAzymes and a novel strategy for activatable NO gas-enhanced mitochondrial gene-photodynamic therapy.
摘要：
新兴研究表明，线粒体DNA是癌症治疗的潜在靶标。然而,实现脱氧核酶（DNAzymes）的精确递送，并将光动力疗法（PDT）和基于DNAzyme的基因沉默结合在一起以增强线粒体基因-光动力协同疗法仍然具有挑战性。因此，在这里，通过将DNAzyme封装到光动力O2省煤器中，构建了智能超分子纳米胶束，用于线粒体NO气体增强的协同基因光动力疗法。设计的纳米胶束表现出敏感的酸和红光序列激活行为。进入癌细胞并靶向线粒体后，这些胶束会在肿瘤微环境中分解和释放DNA酶和Mn(II)卟啉。Mn（II）卟啉充当DNA酶辅因子以激活DNA酶用于裂解反应。随后，携带NO的供体在红光照射下分解产生抑制细胞呼吸的NO，促进肿瘤细胞中更多的O2转化为单态氧（1O2），从而显著提高PDT的疗效。体外和体内实验表明，所提出的系统可以有效地靶向线粒体，并表现出相当大的抗肿瘤作用，全身毒性可忽略不计。因此，这项研究为DNAzymes的精确递送提供了有用的条件平台，并为可激活NO气体增强的线粒体基因光动力疗法提供了新的策略。本文受版权保护。保留所有权利。
