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

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  • ReceivedJul 9, 2019
  • AcceptedSep 22, 2019
  • PublishedNov 7, 2019

Abstract

Organic phosphorescence materials with long-lived 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.


Funded by

the National Key R&D Program of China(2018YFC1105402,2017YFA0207202)

the National Natural Science Foundation of China(21875104,51673095,21875189)

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)


Acknowledgment

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).


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

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.


Author information

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.


Supplement

Supplementary information

Supporting data are available in the online version of the paper.


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  • Figure 1

    (a) Mechanism illustration of photodynamic antimicrobial process of PNPs. (b) TEM image of PNPs. (c) Normalized excitation (black line) and photoluminescence (red line) spectra of PNPs in deionized water. Inset: molecular structure of DBCz-BT. (d) Lifetime decay profile of an emission band at 600 nm of PNPs.

  • Figure 2

    (a) Absorption spectra of ADMA alone, and ADMA with PNPs in PBS buffer under the 410 nm excitation ranging from 0 to 30 min. Inset: plot of function relation of absorbance at 260 nm and irradiation time. (b) The bactericidal efficacy of PNPs at different concentrations towards Gram-negative E. coli and Gram-positive MRSA in log(CFU) (irradiation for 5 min and incubation in dark for 2 h). (c) The bactericidal efficacy of MRSA in log(CFU) of PNPs at 0.8 mg mL–1 with different irradiation times. (d) Images of MRSA growing on agar plates after treatment with and without PNPs for different irradiation times.

  • Figure 3

    In vitro biocompatibility. (a) Percentage viability relative to TCPS control group. Each data point represents the mean ± standard deviation for five separately prepared samples (n=5). LIVE/DEAD fluorescent images of C2C12 cells cultured in the presence of the control group ((b) and (d)) and hydrogel treated group ((c) and (e)) on 1 and 5 days (scale bar: 500 µm).

  • Figure 4

    In vivo anti-infective activity. (a) Photographs of rat burn infective wound model. SEM observation of the skin removed on day 3 to control (b) and treated (c). (d) Number of viable MRSA recovered from the wound skin after 1, 3 days load in the burn wound infective model (n=4, **p<0.001). H&E images of the tissue adjacent to control (e) and treated (f) on day 3 (scale bar: 5 µm).

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