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Human Serum Albumin–Oligothiophene Bioconjugate: A Phototheranostic Platform for Localized Killing of Cancer Cells by Precise Light Activation
JACS Au ( IF 8.5 ) Pub Date : 2021-07-06 , DOI: 10.1021/jacsau.1c00061 Andrea Cantelli 1 , Marco Malferrari 1 , Alice Soldà 1 , Giorgia Simonetti 2 , Sonny Forni 1 , Edoardo Toscanella 1 , Edoardo J Mattioli 1 , Francesco Zerbetto 1 , Alberto Zanelli 3 , Matteo Di Giosia 1 , Mattia Zangoli 3, 4 , Giovanna Barbarella 3, 4 , Stefania Rapino 1 , Francesca Di Maria 3, 4 , Matteo Calvaresi 1
JACS Au ( IF 8.5 ) Pub Date : 2021-07-06 , DOI: 10.1021/jacsau.1c00061 Andrea Cantelli 1 , Marco Malferrari 1 , Alice Soldà 1 , Giorgia Simonetti 2 , Sonny Forni 1 , Edoardo Toscanella 1 , Edoardo J Mattioli 1 , Francesco Zerbetto 1 , Alberto Zanelli 3 , Matteo Di Giosia 1 , Mattia Zangoli 3, 4 , Giovanna Barbarella 3, 4 , Stefania Rapino 1 , Francesca Di Maria 3, 4 , Matteo Calvaresi 1
Affiliation
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The electronic, optical, and redox properties of thiophene-based materials have made them pivotal in nanoscience and nanotechnology. However, the exploitation of oligothiophenes in photodynamic therapy is hindered by their intrinsic hydrophobicity that lowers their biocompatibility and availability in water environments. Here, we developed human serum albumin (HSA)–oligothiophene bioconjugates that afford the use of insoluble oligothiophenes in physiological environments. UV–vis and electrophoresis proved the conjugation of the oligothiophene sensitizers to the protein. The bioconjugate is water-soluble and biocompatible, does not have any “dark toxicity”, and preserves HSA in the physiological monomeric form, as confirmed by dynamic light scattering and circular dichroism measurements. In contrast, upon irradiation with ultralow light doses, the bioconjugate efficiently produces reactive oxygen species (ROS) and leads to the complete eradication of cancer cells. Real-time monitoring of the photokilling activity of the HSA–oligothiophene bioconjugate shows that living cells “explode” upon irradiation. Photodependent and dose-dependent apoptosis is one of the primary mechanisms of cell death activated by bioconjugate irradiation. The bioconjugate is a novel theranostic platform able to generate ROS intracellularly and provide imaging through the fluorescence of the oligothiophene. It is also a real-time self-reporting system able to monitor the apoptotic process. The induced phototoxicity is strongly confined to the irradiated region, showing localized killing of cancer cells by precise light activation of the bioconjugate.
中文翻译：
人血清白蛋白-低聚噻吩生物共轭物：通过精确光激活局部杀死癌细胞的光治疗平台
噻吩基材料的电子、光学和氧化还原特性使其在纳米科学和纳米技术中发挥着关键作用。然而，低聚噻吩在光动力疗法中的应用受到其固有疏水性的阻碍，降低了其在水环境中的生物相容性和可用性。在这里，我们开发了人血清白蛋白（HSA）-低聚噻吩生物缀合物，可在生理环境中使用不溶性低聚噻吩。紫外可见分光光度计和电泳证明了低聚噻吩敏化剂与蛋白质的结合。动态光散射和圆二色性测量证实，该生物结合物是水溶性的且具有生物相容性，不具有任何“暗毒性”，并且以生理单体形式保留HSA。相比之下，在超低光剂量照射下，生物结合物有效地产生活性氧（ROS）并导致癌细胞的完全根除。实时监测 HSA-低聚噻吩生物共轭物的光杀伤活性表明，活细胞在照射后会“爆炸”。光依赖性和剂量依赖性细胞凋亡是生物缀合物辐照激活的细胞死亡的主要机制之一。该生物结合物是一种新型治疗诊断平台，能够在细胞内产生 ROS，并通过寡聚噻吩的荧光提供成像。它也是一个能够监测细胞凋亡过程的实时自我报告系统。诱导的光毒性强烈限制在照射区域，通过生物结合物的精确光激活来局部杀死癌细胞。
更新日期：2021-07-26
中文翻译：
人血清白蛋白-低聚噻吩生物共轭物：通过精确光激活局部杀死癌细胞的光治疗平台
噻吩基材料的电子、光学和氧化还原特性使其在纳米科学和纳米技术中发挥着关键作用。然而，低聚噻吩在光动力疗法中的应用受到其固有疏水性的阻碍，降低了其在水环境中的生物相容性和可用性。在这里，我们开发了人血清白蛋白（HSA）-低聚噻吩生物缀合物，可在生理环境中使用不溶性低聚噻吩。紫外可见分光光度计和电泳证明了低聚噻吩敏化剂与蛋白质的结合。动态光散射和圆二色性测量证实，该生物结合物是水溶性的且具有生物相容性，不具有任何“暗毒性”，并且以生理单体形式保留HSA。相比之下，在超低光剂量照射下，生物结合物有效地产生活性氧（ROS）并导致癌细胞的完全根除。实时监测 HSA-低聚噻吩生物共轭物的光杀伤活性表明，活细胞在照射后会“爆炸”。光依赖性和剂量依赖性细胞凋亡是生物缀合物辐照激活的细胞死亡的主要机制之一。该生物结合物是一种新型治疗诊断平台，能够在细胞内产生 ROS，并通过寡聚噻吩的荧光提供成像。它也是一个能够监测细胞凋亡过程的实时自我报告系统。诱导的光毒性强烈限制在照射区域，通过生物结合物的精确光激活来局部杀死癌细胞。
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