Program in Molecular Genetics, Wake Forest School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Physics, Wake Forest University, Winston-Salem, NC, USA.
Nanomedicine. 2014 Feb;10(2):451-61. doi: 10.1016/j.nano.2013.07.019. Epub 2013 Aug 27.
DNA and porphyrin based therapeutics are important for anti-cancer treatment. The present studies demonstrate single-stranded DNA (ssDNA) assembles with meso-tetra-4-pyridyl porphine (MTP) forming porphyrin:DNA nano-complexes (PDN) that are stable in aqueous solution under physiologically relevant conditions and undergo dissociation with DNA release in hydrophobic environments, including cell membranes. PDN formation is DNA-dependent with the ratio of porphyrin:DNA being approximately two DNA nucleobases per porphyrin. PDN produce reactive oxygen species (ROS) in a light-dependent manner under conditions that favor nano-complex dissociation in the presence of hydrophobic solvents. PDN induce light-dependent cytotoxicity in vitro and anti-tumor activity towards bladder cancer xenografts in vivo. Light-dependent, PDN-mediated cell death results from ROS-mediated localized membrane damage due to lipid peroxidation with mass spectrometry indicating the generation of the lipid peroxidation products 9- and 13-hydroxy octadecanoic acid. Our results demonstrate that PDN have properties useful for therapeutic applications, including cancer treatment.
In this study, porphyrin-DNA nanocomplexes were investigated as anti-cancer therapeutics inducing ROS production in a light-dependent manner. Efficacy is demonstrated in vitro as well as a in a bladder cancer xenograft model.
DNA 和基于卟啉的治疗方法对于癌症治疗很重要。本研究表明，单链 DNA（ssDNA）与中四-4-吡啶卟啉（MTP）组装形成卟啉：DNA 纳米复合物（PDN），在生理相关条件下在水溶液中稳定，并且在疏水环境中解离并释放 DNA，包括细胞膜。PDN 的形成是 DNA 依赖性的，卟啉：DNA 的比例约为每个卟啉两个 DNA 核碱基。在有利于疏溶剂存在下纳米复合物解离的条件下，PDN 以光依赖性方式产生活性氧物质（ROS）。PDN 在体外诱导光依赖性细胞毒性，并在体内对膀胱癌异种移植物具有抗肿瘤活性。光依赖性、PDN 介导的细胞死亡是由于脂质过氧化导致局部膜损伤所致，质谱分析表明脂质过氧化产物 9-和 13-羟基十八烷酸的生成。我们的研究结果表明，PDN 具有用于治疗应用的特性，包括癌症治疗。
在这项研究中，研究了卟啉-DNA 纳米复合物作为光依赖性诱导 ROS 产生的抗癌治疗剂。在体外和膀胱癌异种移植模型中均证明了疗效。
