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ROS generation/scavenging modulation of carbon dots as phototherapeutic candidates and peroxidase mimetics to integrate with polydopamine nanoparticles/GOx towards cooperative cancer therapy
Composites Part B: Engineering ( IF 12.7 ) Pub Date : 2021-09-27 , DOI: 10.1016/j.compositesb.2021.109364
Girum Getachew, Chiranjeevi Korupalli, Akash S. Rasal, Jia-Yaw Chang

In this study, the reactive oxygen species (ROS) scavenging or generation ability of the carbon dots (CDs) was regulated by incorporating with heteroatoms (Cu and Cl ions). The pristine CDs were found to be powerful anti-oxidants to scavenge ROS, with half-maximal inhibitory concentrations (IC50) of O2 and OH radicals estimated to be 6.89 and 6.12 μg/mL, respectively, whereas Cu and Cl co-doped CDs (CuCl-CDs) possessed not only ROS generation ability upon laser irradiation for photodynamic therapy (PDT), but also peroxidase-mimic activity that generates oxidative •OH from hydrogen peroxide (H2O2) for chemodynamic therapy (CDT). Moreover, the colorimetric assay, 1O2 emission peak, and ESR results supported the efficient production of •O2, •OH, and 1O2 radicals. Furthermore, CuCl-CDs with ROS-generating abilities and peroxidase-mimetic properties were successfully integrated with polydopamine (PDA) and glucose oxidase (GOx) to fabricate multifunctional GOx/CuCl-CD@PDA-PEG (GCP) nanocomposites with hydrodynamic sizes of 135.5 nm. These novel GCP nanocomposites possessed satisfactory photothermal conversion efficacies (η = 24.4%) and gave a high yield of ROS via the combination of H2O2 and laser irradiation. Moreover, the presence of GOx in GCP nanocomposites enables these compounds to decrease the intracellular glucose levels for starvation therapy and the enzymatic cascade activity for enhanced ROS-mediated therapy. In vitro studies and confirmed that these GCP nanocomposites displayed good biocompatibility with concentrations from 100 to 1000 ppm, but induced 90% reduction in B16F1 cell viability at 200 ppm via the cooperative effects of CDT, phototherapeutic effect, and starvation therapy.



中文翻译:

碳点作为光治疗候选物和过氧化物酶模拟物的 ROS 生成/清除调节与聚多巴胺纳米颗粒/GOx 整合以实现协同癌症治疗

在这项研究中,碳点 (CD) 的活性氧 (ROS) 清除或生成能力通过与杂原子 (Cu 和 Cl 离子) 结合来调节。原始 CD 被发现是清除 ROS 的强大抗氧化剂,其中 O 2 - OH 自由基的半数最大抑制浓度 (IC50)估计分别为 6.89 和 6.12 μg/mL,而 Cu 和 Cl co掺杂的 CDs (CuCl-CDs) 不仅在用于光动力疗法 (PDT) 的激光照射下具有 ROS 生成能力,而且还具有用于化学动力疗法 (CDT)从过氧化氢 (H 2 O 2 )生成氧化性·OH 的过氧化物酶模拟活性. 此外,比色测定,1 O2发射峰,ESR 结果支持•O 2 -、•OH 和1 O 2自由基的有效生产。此外,具有 ROS 生成能力和过氧化物酶模拟特性的 CuCl-CDs 成功地与聚多巴胺 (PDA) 和葡萄糖氧化酶 (GOx) 结合,以制备流体力学尺寸为 135.5 的多功能 GOx/CuCl-CD@PDA-PEG (GCP) 纳米复合材料纳米。这些新型 GCP 纳米复合材料具有令人满意的光热转化效率 (η = 24.4%) 并通过 H 2 O 2的组合产生高产率和激光照射。此外,GCP 纳米复合材料中 GOx 的存在使这些化合物能够降低饥饿治疗的细胞内葡萄糖水平和增强 ROS 介导治疗的酶促级联活性。体外研究证实,这些 GCP 纳米复合材料在 100 至 1000 ppm 的浓度下显示出良好的生物相容性,但通过 CDT、光疗效应和饥饿疗法的协同作用,在 200 ppm 时诱导 B16F1 细胞活力降低 90%。

更新日期:2021-10-01
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