Abstract:
The contrast agents and tumor treatments currently used in clinical practice are far from satisfactory, due to the specificity of the tumor microenvironment (TME). Identification of diagnostic and therapeutic reagents with strong contrast and therapeutic effect remains a great challenge. Herein, a novel carbon dot nanozyme (Mn-CD) is synthesized for the first time using toluidine blue (TB) and manganese as raw materials. As expected, the enhanced magnetic resonance (MR) imaging capability of Mn-CDs is realized in response to the TME (acidity and glutathione), and r1 and r2 relaxation rates are enhanced by 224% and 249%, respectively. In addition, the photostability of Mn-CDs is also improved, and show an efficient singlet oxygen (1 O2 ) yield of 1.68. Moreover, Mn-CDs can also perform high-efficiency peroxidase (POD)-like activity and catalyze hydrogen peroxide to hydroxyl radicals, which is greatly improved under the light condition. The results both in vitro and in vivo demonstrate that the Mn-CDs are able to achieve real-time MR imaging of TME responsiveness through aggregation of the enhanced permeability and retention effect at tumor sites and facilitate light-enhanced chemodynamic and photodynamic combination therapies. This work opens a new perspective in terms of the role of carbon nanomaterials in integrated diagnosis and treatment of diseases.
摘要:
目前临床上使用的造影剂和肿瘤治疗方法远不能令人满意,由于肿瘤微环境(TME)的特异性。鉴定具有强对比和治疗效果的诊断和治疗试剂仍然是一个巨大的挑战。在这里,以甲苯胺蓝(TB)和锰为原料,首次合成了一种新型碳点纳米酶(Mn-CD)。不出所料,响应于TME(酸度和谷胱甘肽),实现了Mn-CD的增强磁共振(MR)成像能力,r1和r2的弛豫率分别提高了224%和249%,分别。此外,Mn-CD的光稳定性也得到改善,并显示出1.68的有效单线态氧(1O2)产率。此外,Mn-CD还可以执行高效过氧化物酶(POD)样活性,并催化过氧化氢生成羟基自由基,在光照条件下大大提高。体外和体内的结果表明,Mn-CD能够通过在肿瘤部位处增强的渗透性和保留效应的聚集来实现TME响应性的实时MR成像,并且促进光增强的化学动力学和光动力学组合疗法。这项工作为碳纳米材料在疾病综合诊断和治疗中的作用开辟了新的视角。