Department of Health Technology, DTU Health Tech, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark; Department of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Department of Inorganic and Physical Chemistry (IPC), Indian Institute of Science (IISc), Bangalore 560012, India.
Colloids Surf B Biointerfaces. 2024 Apr;236:113790. doi: 10.1016/j.colsurfb.2024.113790. Epub 2024 Feb 7.
This work introduces novel nitroxide-based nanogels (NGs) crafted through controlled RAFT (Reversible Addition Fragmentation chain Transfer) polymerization, showcasing over 85% improved shelf-life compared to native superoxide dismutase (SOD) enzymes. These 30-40 nm NGs hold great promise for injectable delivery, effectively reducing foam cell formation and displaying potent antioxidant behavior against various reactive oxygen species (ROS), revolutionizing antioxidant therapy. Featuring a meticulously designed core-shell structure via precise RAFT polymerization, these NGs mimic SOD enzymatic activity with nitroxide-based antioxidants, providing unprecedented defense against ROS. Combining methacrylated 2,2,6,6-Tetramethyl-4-piperidyl methacrylate (PMA) and Glycidyl methacrylate (GMA) monomers with precisely synthesized nitroxyl radicals results in exceptional properties. Validated through comprehensive analytical methods, these NGs exhibit remarkable stability, halting foam cell formation even at high concentrations, and demonstrate notable biocompatibility. Their ability to protect low density lipoprotein (LDL) from oxidation for up to a month positions them at the forefront of combating cardiovascular diseases, especially atherosclerosis. This study pioneers injectable antioxidant therapy, offering an innovative approach to cardiovascular ailments. Targeting narrow plaques signifies a promising intervention, reshaping cardiovascular disease treatments. It highlights the potential of advanced drug delivery in biomedicine, promising more effective cardiovascular disease treatments.
这项工作介绍了通过可控 RAFT（可逆加成断裂链转移）聚合制备的新型氮氧自由基纳米凝胶（NGs），与天然超氧化物歧化酶（SOD）相比，其货架寿命提高了 85%以上。这些 30-40nm 的 NGs 具有很大的注射递药潜力，可有效减少泡沫细胞的形成，并对各种活性氧（ROS）表现出强大的抗氧化行为，彻底改变了抗氧化治疗。通过精确的 RAFT 聚合形成精心设计的核壳结构，这些 NGs 通过氮氧自由基类抗氧化剂模拟 SOD 的酶活性，为 ROS 提供前所未有的防御。将甲基丙烯酰化 2,2,6,6-四甲基-4-哌啶基甲基丙烯酸酯（PMA）和甲基丙烯酸缩水甘油酯（GMA）单体与精确合成的氮氧自由基结合，产生了卓越的性能。通过全面的分析方法进行验证，这些 NGs 表现出显著的稳定性，即使在高浓度下也能阻止泡沫细胞的形成，并且表现出良好的生物相容性。它们能够保护低密度脂蛋白（LDL）免受氧化长达一个月，这使它们成为对抗心血管疾病，特别是动脉粥样硬化的前沿药物。这项研究开创了可注射抗氧化治疗的先河，为心血管疾病提供了一种创新的治疗方法。靶向狭窄斑块是一种很有前途的干预手段，为心血管疾病的治疗带来了新的可能。它突显了先进药物输送在生物医学中的潜力，为更有效的心血管疾病治疗提供了可能。
