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

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


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)


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.


Supplementary information

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


[1] Kabe R, Notsuka N, Yoshida K, et al. Afterglow organic light-emitting diode. Adv Mater, 2016, 28: 655-660 CrossRef PubMed Google Scholar

[2] Zhen X, Tao Y, An Z, et al. Ultralong phosphorescence of water-soluble organic nanoparticles for in vivo afterglow imaging. Adv Mater, 2017, 29: 1606665-1606671 CrossRef PubMed Google Scholar

[3] Fateminia SMA, Mao Z, Xu S, et al. Organic nanocrystals with bright red persistent room-temperature phosphorescence for biological applications. Angew Chem Int Ed, 2017, 56: 12160-12164 CrossRef PubMed Google Scholar

[4] Shi H, Ma X, Zhao Q, et al. Ultrasmall phosphorescent polymer dots for ratiometric oxygen sensing and photodynamic cancer therapy. Adv Funct Mater, 2014, 24: 4823-4830 CrossRef Google Scholar

[5] DeRosa CA, Seaman SA, Mathew AS, et al. Oxygen sensing difluoroboron β-diketonate polylactide materials with tunable dynamic ranges for wound imaging. ACS Sens, 2016, 1: 1366-1373 CrossRef Google Scholar

[6] Lehner P, Staudinger C, Borisov SM, et al. Ultra-sensitive optical oxygen sensors for characterization of nearly anoxic systems. Nat Commun, 2015, 5: 4460-4466 CrossRef PubMed ADS Google Scholar

[7] Cheng Z, Shi H, Ma H, et al. Ultralong phosphorescence from organic ionic crystals under ambient conditions. Angew Chem Int Ed, 2018, 57: 678-682 CrossRef PubMed Google Scholar

[8] Wu Q, Ma H, Ling K, et al. Reversible ultralong organic phosphorescence for visual and selective chloroform detection. ACS Appl Mater Interfaces, 2018, 10: 33730-33736 CrossRef Google Scholar

[9] Yang Z, Mao Z, Zhang X, et al. Intermolecular electronic coupling of organic units for efficient persistent room-temperature phosphorescence. Angew Chem Int Ed, 2016, 55: 2181-2185 CrossRef PubMed Google Scholar

[10] Wei J, Liang B, Duan R, et al. Induction of strong long-lived room-temperature phosphorescence of N-phenyl-2-naphthylamine molecules by confinement in a crystalline dibromobiphenyl matrix. Angew Chem Int Ed, 2016, 55: 15589-15593 CrossRef PubMed Google Scholar

[11] Yu Z, Wu Y, Xiao L, et al. Organic phosphorescence nanowire lasers. J Am Chem Soc, 2017, 139: 6376-6381 CrossRef PubMed Google Scholar

[12] Hirata S, Totani K, Yamashita T, et al. Large reverse saturable absorption under weak continuous incoherent light. Nat Mater, 2014, 13: 938-946 CrossRef PubMed ADS Google Scholar

[13] Lo KKW, Louie MW, Zhang KY. Design of luminescent iridium(III) and rhenium(I) polypyridine complexes as in vitro and in vivo ion, molecular and biological probes. Coord Chem Rev, 2010, 254: 2603-2622 CrossRef Google Scholar

[14] Schulte TR, Holstein JJ, Krause L, et al. Chiral-at-metal phosphorescent square-planar Pt(II)-complexes from an achiral organometallic ligand. J Am Chem Soc, 2017, 139: 6863-6866 CrossRef PubMed Google Scholar

[15] Xia Z, Meijerink A. Ce3+-doped garnet phosphors: Composition modification, luminescence properties and applications. Chem Soc Rev, 2017, 46: 275-299 CrossRef PubMed Google Scholar

[16] Xu H, Chen R, Sun Q, et al. Recent progress in metal-organic complexes for optoelectronic applications. Chem Soc Rev, 2014, 43: 3259-3302 CrossRef PubMed Google Scholar

[17] An Z, Zheng C, Tao Y, et al. Stabilizing triplet excited states for ultralong organic phosphorescence. Nat Mater, 2015, 14: 685-690 CrossRef PubMed ADS Google Scholar

[18] Shi H, Song L, Ma H, et al. Highly efficient ultralong organic phosphorescence through intramolecular-space heavy-atom effect. J Phys Chem Lett, 2019, 10: 595-600 CrossRef PubMed Google Scholar

[19] Cai S, Shi H, Li J, et al. Visible-light-excited ultralong organic phosphorescence by manipulating intermolecular interactions. Adv Mater, 2017, 29: 1701244-1701249 CrossRef PubMed Google Scholar

[20] Gu L, Shi H, Gu M, et al. Dynamic ultralong organic phosphorescence by photoactivation. Angew Chem Int Ed, 2018, 57: 8425-8431 CrossRef PubMed Google Scholar

[21] Cai S, Shi H, Zhang Z, et al. Hydrogen-bonded organic aromatic frameworks for ultralong phosphorescence by intralayer π-π interactions. Angew Chem Int Ed, 2018, 57: 4005-4009 CrossRef PubMed Google Scholar

[22] Gu L, Shi H, Bian L, et al. Colour-tunable ultra-long organic phosphorescence of a single-component molecular crystal. Nat Photonics, 2019, 13: 406-411 CrossRef ADS Google Scholar

[23] Gu L, Shi H, Miao C, et al. Prolonging the lifetime of ultralong organic phosphorescence through dihydrogen bonding. J Mater Chem C, 2018, 6: 226-233 CrossRef Google Scholar

[24] Cai S, Shi H, Tian D, et al. Enhancing ultralong organic phosphorescence by effective π-type halogen bonding. Adv Funct Mater, 2018, 28: 1705045-1705051 CrossRef Google Scholar

[25] Yuan WZ, Shen XY, Zhao H, et al. Crystallization-induced phosphorescence of pure organic luminogens at room temperature. J Phys Chem C, 2010, 114: 6090-6099 CrossRef Google Scholar

[26] Bolton O, Lee K, Kim HJ, et al. Activating efficient phosphorescence from purely organic materials by crystal design. Nat Chem, 2011, 3: 205-210 CrossRef PubMed ADS Google Scholar

[27] Yang J, Zhen X, Wang B, et al. The influence of the molecular packing on the room temperature phosphorescence of purely organic luminogens. Nat Commun, 2018, 9: 840-849 CrossRef PubMed ADS Google Scholar

[28] Chen J, Yu T, Ubba E, et al. Achieving dual-emissive and time-dependent evolutive organic afterglow by bridging molecules with weak intermolecular hydrogen bonding. Adv Opt Mater, 2019, 7: 1801593-1801599 CrossRef Google Scholar

[29] Bian L, Shi H, Wang X, et al. Simultaneously enhancing efficiency and lifetime of ultralong organic phosphorescence materials by molecular self-assembly. J Am Chem Soc, 2018, 140: 10734-10739 CrossRef PubMed Google Scholar

[30] Hirata S, Totani K, Zhang J, et al. Efficient persistent room temperature phosphorescence in organic amorphous materials under ambient conditions. Adv Funct Mater, 2013, 23: 3386-3397 CrossRef Google Scholar

[31] Kwon MS, Lee D, Seo S, et al. Tailoring intermolecular interactions for efficient room-temperature phosphorescence from purely organic materials in amorphous polymer matrices. Angew Chem Int Ed, 2014, 53: 11177-11181 CrossRef PubMed Google Scholar

[32] Louis M, Thomas H, Gmelch M, et al. Blue-light-absorbing thin films showing ultralong room-temperature phosphorescence. Adv Mater, 2019, 31: 1807887-1807891 CrossRef PubMed Google Scholar

[33] Hirata S, Vacha M. White afterglow room-temperature emission from an isolated single aromatic unit under ambient condition. Adv Opt Mater, 2017, 5: 1600996-1601006 CrossRef Google Scholar

[34] Ogoshi T, Tsuchida H, Kakuta T, et al. Ultralong room-temperature phosphorescence from amorphous polymer poly(styrene sulfonic acid) in air in the dry solid state. Adv Funct Mater, 2018, 28: 1707369-1707375 CrossRef Google Scholar

[35] Zhang G, Palmer GM, Dewhirst MW, et al. A dual-emissive-materials design concept enables tumour hypoxia imaging. Nat Mater, 2009, 8: 747-751 CrossRef PubMed ADS Google Scholar

[36] Chen H, Yao X, Ma X, et al. Amorphous, efficient, room-temperature phosphorescent metal-free polymers and their applications as encryption ink. Adv Opt Mater, 2016, 4: 1397-1401 CrossRef Google Scholar

[37] Ma X, Xu C, Wang J, et al. Amorphous pure organic polymers for heavy-atom-free efficient room-temperature phosphorescence emission. Angew Chem, 2018, 130: 11020-11024 CrossRef Google Scholar

[38] Koch M, Perumal K, Blacque O, et al. Metal-free triplet phosphors with high emission efficiency and high tunability. Angew Chem Int Ed, 2014, 53: 6378-6382 CrossRef PubMed Google Scholar

[39] Yang J, Ren Z, Xie Z, et al. AIEgen with fluorescence-phosphorescence dual mechanoluminescence at room temperature. Angew Chem Int Ed, 2017, 56: 880-884 CrossRef PubMed Google Scholar

[40] Wang XF, Xiao H, Chen PZ, et al. Pure organic room temperature phosphorescence from excited dimers in self-assembled nanoparticles under visible and near-infrared irradiation in water. J Am Chem Soc, 2019, 141: 5045-5050 CrossRef PubMed Google Scholar

[41] Wang J, Gu X, Ma H, et al. A facile strategy for realizing room temperature phosphorescence and single molecule white light emission. Nat Commun, 2018, 9: 2963-2971 CrossRef PubMed ADS Google Scholar

[42] Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: The who priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis, 2018, 18: 318-327 CrossRef Google Scholar

[43] Christou A, Agüera A, Bayona JM, et al. The potential implications of reclaimed wastewater reuse for irrigation on the agricultural environment: The knowns and unknowns of the fate of antibiotics and antibiotic resistant bacteria and resistance genes—A review. Water Res, 2017, 123: 448-467 CrossRef PubMed Google Scholar

[44] Kumar P, Kizhakkedathu JN, Straus SK. Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules, 2018, 8: 4 CrossRef PubMed Google Scholar

[45] Zhang D, Qian Y, Zhang S, et al. Alpha-beta chimeric polypeptide molecular brushes display potent activity against superbugs-methicillin resistant staphylococcus aureus. Sci China Mater, 2019, 62: 604-610 CrossRef Google Scholar

[46] Fumery M, Singh S, Dulai PS, et al. Natural history of adult ulcerative colitis in population-based cohorts: A systematic review. Clin Gastroenterol Hepatol, 2018, 16: 343-356 CrossRef PubMed Google Scholar

[47] Miller-Ensminger T, Garretto A, Brenner J, et al. Bacteriophages of the urinary microbiome. J Bacteriol, 2018, 200: 365-373 CrossRef PubMed Google Scholar

[48] Zheng K, Setyawati MI, Leong DT, et al. Antimicrobial silver nanomaterials. Coord Chem Rev, 2018, 357: 1-17 CrossRef Google Scholar

[49] Lam SJ, O'Brien-Simpson NM, Pantarat N, et al. Combating multidrug-resistant gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat Microbiol, 2016, 1: 16162 CrossRef PubMed Google Scholar

[50] Panáček A, Kvítek L, Smékalová M, et al. Bacterial resistance to silver nanoparticles and how to overcome it. Nat Nanotech, 2018, 13: 65-71 CrossRef PubMed ADS Google Scholar

[51] Klose CSN, Artis D. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat Immunol, 2016, 17: 765-774 CrossRef PubMed Google Scholar

[52] Lu LL, Suscovich TJ, Fortune SM, et al. Beyond binding: Antibody effector functions in infectious diseases. Nat Rev Immunol, 2018, 18: 46-61 CrossRef PubMed Google Scholar

[53] Li Y, Liu X, Tan L, et al. Rapid sterilization and accelerated wound healing using Zn2+ and graphene oxide modified g-C3N4 under dual light irradiation. Adv Funct Mater, 2018, 28: 1800299-1800310 CrossRef Google Scholar

[54] Zhang X, Xia LY, Chen X, et al. Hydrogel-based phototherapy for fighting cancer and bacterial infection. Sci China Mater, 2017, 60: 487-503 CrossRef Google Scholar

[55] Zhang M, Zhang C, Zhai X, et al. Antibacterial mechanism and activity of cerium oxide nanoparticles. Sci China Mater, 2019, 58: 1-13 CrossRef Google Scholar

[56] Yuan H, Chong H, Wang B, et al. Chemical molecule-induced light-activated system for anticancer and antifungal activities. J Am Chem Soc, 2012, 134: 13184-13187 CrossRef PubMed Google Scholar

[57] Liu K, Liu Y, Yao Y, et al. Supramolecular photosensitizers with enhanced antibacterial efficiency. Angew Chem Int Ed, 2013, 52: 8285-8289 CrossRef PubMed Google Scholar

[58] Shi H, Zou L, Huang K, et al. A highly efficient red metal-free organic phosphor for time-resolved luminescence imaging and photodynamic therapy. ACS Appl Mater Interfaces, 2019, 11: 18103-18110 CrossRef Google Scholar

[59] Ogilby PR. Singlet oxygen: There is indeed something new under the sun. Chem Soc Rev, 2010, 39: 3181-3209 CrossRef PubMed Google Scholar

[60] Ma X, Sreejith S, Zhao Y. Spacer intercalated disassembly and photodynamic activity of zinc phthalocyanine inside nanochannels of mesoporous silica nanoparticles. ACS Appl Mater Interfaces, 2013, 5: 12860-12868 CrossRef PubMed Google Scholar

[61] Kawesa S, Vanstone J, Tsilfidis C. A differential response to newt regeneration extract by C2C12 and primary mammalian muscle cells. Skeletal Muscle, 2015, 5: 19-34 CrossRef PubMed Google Scholar

[62] Mofazzal Jahromi MA, Sahandi Zangabad P, Moosavi Basri SM, et al. Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing. Adv Drug Deliver Rev, 2018, 123: 33-64 CrossRef PubMed Google Scholar

[63] Fitzwater J, Purdue GF, Hunt JL, et al. The risk factors and time course of sepsis and organ dysfunction after burn trauma. J Trauma-Injury Infection Critical Care, 2003, 54: 959-966 CrossRef PubMed Google Scholar

[64] Miao Q, Xie C, Zhen X, et al. Molecular afterglow imaging with bright, biodegradable polymer nanoparticles. Nat Biotechnol, 2017, 35: 1102-1110 CrossRef PubMed Google Scholar

  • 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).


Contact and support