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Biocompatible metal-free organic phosphorescent nanoparticles for efficiently multidrug-resistant bacteria eradication

具有生物相容性的纯有机磷光纳米粒子有效杀灭 耐药细菌

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Abstract

Organic phosphorescence materials with longlived triplet excitons that can highly generate active singlet oxygen (1O2) through the energy transfer with the molecular oxygen under photoexcitation, serve as highly efficient antibacterial agent. Herein, we report bright red-emissive organic phosphorescent nanoparticles (PNPs) based on a metal-free organic phosphor encapsulated with biocompatible block copolymers. The obtained PNPs with an ultra-small particle size of around 5 nm and a long emission lifetime of up to 167 µs showed effective 1O2 generation ability under visible light (410 nm) excitation in aqueous media, which can efficiently eradicate multi-drug resistant bacteria both in vitro and in vivo. This is the first demonstration of metal-free organic PNPs for photodynamic antimicrobial therapy, expanding the application scope of metal-free organic room temperature phosphorescent materials.

摘要

具有长寿命三线态激子的有机磷光材料在光激发下, 通过与 分子氧的能量传递可产生高活性的单线态氧(1O2), 该单线态氧具 有抗菌能力. 然而, 传统的有机金属磷光材料的高毒性严重限制了 它们在生物医学领域的实际应用. 相较于金属有机材料, 不含金属 的纯有机磷光纳米粒子具有良好的水分散性和生物相容性, 可作 为抗菌材料被重点研究. 本文以无金属有机磷光粉DBCz-BT(4,7- 二溴-5,6-二(9H-咔唑-9-酰基)苯并[c][1,2,5]噻二唑)为原料, 并利用 具有生物相容性的嵌段共聚物将其包裹, 成功制备了具有红色室 温磷光发射的纳米粒子. 该纳米粒子分散在水溶液中的粒径约为 5 nm, 磷光寿命可达167 μs, 同时具有高效的单线态氧产生能力. 这些独特的性质使得该纳米粒子可以在体外和体内有效地杀灭多 重耐药细菌. 本文首次将无金属纯有机磷光纳米粒子用于光动力 抗菌 治疗领域, 扩大了无金属有机室温磷光材料的应用范围.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2018YFC1105402 and 2017YFA0207202), the National Natural Science Foundation of China (21975120, 21875104, 51673095 and 21875189), the National Basic Research Program of China (973 Program, 2015CB932200), the Natural Science Fund for Distinguished Young Scholars of Jiangsu Province (BK20180037), the Natural Science Fund for Colleges and Universities of Jiangsu Province (17KJB430020), and the Key R&D Program of Jiangsu Province (BE2017740).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing, 211816, China

    Shan Wang  (王姗), Miao Xu  (徐淼), Kaiwei Huang  (黄凯薇), Jiahuan Zhi  (支佳欢), Chen Sun  (孙晨), Kai Wang  (王楷), Qian Zhou  (周倩), Lingling Gao  (高玲玲), Huifang Shi  (史慧芳), Zhongfu An  (安众福), Peng Li  (李鹏) & Wei Huang  (黄维)

  2. Xi’an Institute of Flexible Electronics (IFE) & Xi’an Institute of Biomedical Materials Engineering (IBME), Northwestern Polytechnical University (NPU), Xi’an, 710072, China

    Qingyan Jia  (贾庆岩), Peng Li  (李鹏) & Wei Huang  (黄维)

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  1. Shan Wang  (王姗)
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  2. Miao Xu  (徐淼)
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  3. Kaiwei Huang  (黄凯薇)
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  5. Chen Sun  (孙晨)
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  6. Kai Wang  (王楷)
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Contributions

Author contributions Shi H, An Z, Li P and Huang W conceived the experiments. Wang S and Xu M wrote the manuscript. Shi H, Zhou Q, Li P, An Z and Huang W revised the manuscript. Wang S, Xu M, Huang K, Sun C, Wang K, Zhi J, Zhou Q, Gao L and Jia Q were primarily responsible for the experiments. Huang K and Zhou Q conducted the TEM measurement and analysis. Sun C, Zhi J and Wang K supplemented the raw materials. Gao L and Jia Q performed the animal experiment. All authors contributed to the data analyses.

Corresponding authors

Correspondence to Huifang Shi  (史慧芳), Zhongfu An  (安众福) or Peng Li  (李鹏).

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Conflict of interest The authors declare that they have no conflict of interest.

Shan Wang received her BSc from the Department of Chemical Engineering and Technology of Nanjing Tech University in 2016. And then she received her MSc under the supervision of Prof. Wei Huang and Prof. Zhongfu An in Nanjing Tech University. Her research focuses on the preparation of ultralong organic phosphorescent materials and phosphorescent nanomaterials for biological applications.

Miao Xu received his BSc from the School of Life Sciences of Tai Zhou University in 2016. And then he received his MSc under the supervision of Prof. Xiao Huang and Prof. Peng Li in Nanjing Tech University. His research focuses on the preparation of multi-functional antimicrobial materials for biological applications.

Huifang Shi received her BSc and BA from Qingdao University of Science & Technology in China in 2008, PhD from Nanjing University of Posts and Telecommunications in 2013. Then she went to Nanyang Technological University in Singapore as a research fellow. She joined the Institute of Advanced Materials (IAM), Nanjing Tech University in 2015 as an Associate Professor. Her present research focuses on organic phosphorescent functional materials for sensing, bioimaging and cancer therapy.

Zhongfu An received his PhD from Nanjing University of Posts and Telecommunications in 2014. After graduation, he went to National University of Singapore for a post-doctoral research in the Department of Chemistry. In 2015, he joined the IAM, Nanjing Tech University. He was promoted exceptionally as a full professor in 2016. His research interest focuses on organic electronics, including organic optoelectronic materials and devices; ultralong organic phosphorescent materials and applications.

Peng Li is a professor at Northwestern Polytechnical University in China. He received his BE from Tianjin University in 2006 and PhD from Nanyang Technological University in 2013. In 2018, Prof. Li joined the Institute of Flexible Electronics (IFE) at Northwestern Polytechnical University. The primary goal of his research team is to develop innovative antibacterial materials and strategies for infection treatments

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Wang, S., Xu, M., Huang, K. et al. Biocompatible metal-free organic phosphorescent nanoparticles for efficiently multidrug-resistant bacteria eradication. Sci. China Mater. 63, 316–324 (2020). https://doi.org/10.1007/s40843-019-1191-9

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