Synergistic Photothermal and Photodynamic Therapy for Effective Implant-Related Bacterial Infection Elimination and Biofilm Disruption Using Cu9S8 Nanoparticles.

Implant-related bacterial infections are one of the most common but tricky problems in orthopedic clinics because the formation of biofilms inhibits the penetration of antibiotics to kill bacteria effectively; thus, a new strategy is urgently needed. Antibacterial nanomaterials [e.g., copper (Cu)-based nanoparticles (NPs)] combined with near-infrared (NIR) irradiation show enhanced antibacterial activity against clinical bacteria. However, their antibacterial efficiency toward implant-related infections and against biofilm formation remains unclear. Here, unique polyethylene glycol-modified Cu9S8 NPs with good biocompatibility were synthesized. We found that the Cu9S8 NPs exhibited high photothermal performance and could increase the generation of reactive oxygen species under NIR irradiation (808 nm, 1 W cm-2). The Cu9S8 NPs with NIR irradiation successfully destroyed the bacterial structure, resulting in the death of the clinically derived Staphylococcus aureus growing on titanium (Ti) plates. Moreover, this excellent antibacterial activity was indicated to have a synergistic effect with photothermal therapy (PTT) and photodynamic therapy (PDT) by comparison to Cu9S8 with heating treatment in a water bath with similar temperature changes compared to NIR + Cu9S8. Finally, the biofilm formation on the Ti plates was effectively disrupted by NIR + Cu9S8 treatment, while Cu9S8 with thermal treatment showed a mild impact. Hence, Cu9S8 NP-based PTT and PDT can provide a promising approach to eliminating implant-related bacteria and disrupting bacterial biofilms.

[1]  Kai Yang,et al.  Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy. , 2014, ACS nano.

[2]  C. Li,et al.  The antifungal activity of graphene oxide-silver nanocomposites. , 2013, Biomaterials.

[3]  Carla Renata Arciola,et al.  Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials. , 2012, Biomaterials.

[4]  M. Peng,et al.  Actively Targeted Deep Tissue Imaging and Photothermal‐Chemo Therapy of Breast Cancer by Antibody‐Functionalized Drug‐Loaded X‐Ray‐Responsive Bismuth Sulfide@Mesoporous Silica Core–Shell Nanoparticles , 2018, Advanced functional materials.

[5]  Zefeng Lin,et al.  Zero-Dimensional Carbon Dots Enhance Bone Regeneration, Osteosarcoma Ablation, and Clinical Bacterial Eradication. , 2018, Bioconjugate chemistry.

[6]  R. Ikeda,et al.  Bacterial and H2O2 stress-induced apoptosis-like events in Cryptococcus neoformans. , 2008, Research in microbiology.

[7]  I. Kraljić,et al.  A NEW METHOD FOR THE DETECTION OF SINGLET OXYGEN IN AQUEOUS SOLUTIONS , 1978 .

[8]  Dong Liang,et al.  CuS Nanodots with Ultrahigh Efficient Renal Clearance for Positron Emission Tomography Imaging and Image-Guided Photothermal Therapy. , 2015, ACS nano.

[9]  Yu-Chie Chen,et al.  Antibacterial gold nanoparticle-based photothermal killing of vancomycin-resistant bacteria. , 2018, Nanomedicine.

[10]  T. Coradin,et al.  Collagen-silica nanocomposites as dermal dressings preventing infection in vivo. , 2018, Materials science & engineering. C, Materials for biological applications.

[11]  Xiaoming Yang,et al.  Exploring the Antibacteria Performance of Multicolor Ag, Au, and Cu Nanoclusters. , 2019, ACS applied materials & interfaces.

[12]  Livia Visai,et al.  POLITECNICO DI TORINO Repository ISTITUZIONALE Copper-containing mesoporous bioactive glass nanoparticles as multifunctional agent for bone regeneration / , 2022 .

[13]  T. Foster,et al.  Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells , 2009, BMC Microbiology.

[14]  Ke Yang,et al.  Toward a Molecular Understanding of the Antibacterial Mechanism of Copper‐Bearing Titanium Alloys against Staphylococcus aureus , 2016, Advanced healthcare materials.

[15]  M. Frieri,et al.  Antibiotic Resistance , 2012, Handbook of Experimental Pharmacology.

[16]  Lei Chen,et al.  Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity. , 2013, Biomaterials.

[17]  Yuan Ping,et al.  Laser-Activatable CuS Nanodots to Treat Multidrug-Resistant Bacteria and Release Copper Ion to Accelerate Healing of Infected Chronic Nonhealing Wounds , 2019, ACS applied materials & interfaces.

[18]  P. Ajayan,et al.  Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents. , 2015, Nanoscale.

[19]  F. Qu,et al.  Hollow CuS nanocube as nanocarrier for synergetic chemo/photothermal/photodynamic therapy. , 2019, Materials science & engineering. C, Materials for biological applications.

[20]  Chengcheng Zhang,et al.  Multifunctional CuS nanocrystals for inhibiting both osteosarcoma proliferation and bacterial infection by photothermal therapy , 2017, Journal of Nanoparticle Research.

[21]  Lijun Lin,et al.  A New Treatment Modality for Rheumatoid Arthritis: Combined Photothermal and Photodynamic Therapy Using Cu7.2S4 Nanoparticles , 2018, Advanced healthcare materials.

[22]  Jinshun Zhao,et al.  A Near Infrared Light Triggered Hydrogenated Black TiO2 for Cancer Photothermal Therapy , 2015, Advanced healthcare materials.

[23]  Juan C. Scaiano,et al.  The biocompatibility and antibacterial properties of collagen-stabilized, photochemically prepared silver nanoparticles. , 2012, Biomaterials.

[24]  S. Gorman,et al.  Biomolecular mechanisms of staphylococcal biofilm formation. , 2013, Future microbiology.

[25]  E. Stride,et al.  Ultrasound‐activated microbubbles as a novel intracellular drug delivery system for urinary tract infection , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[26]  V. Rotello,et al.  Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms. , 2015, ACS nano.

[27]  Hongwei Song,et al.  Noninvasive temperature monitoring for dual-modal tumor therapy based on lanthanide-doped up-conversion nanocomposites. , 2019, Biomaterials.

[28]  R. Haag,et al.  Construction of Functional Coatings with Durable and Broad-Spectrum Antibacterial Potential Based on Mussel-Inspired Dendritic Polyglycerol and in Situ-Formed Copper Nanoparticles. , 2017, ACS applied materials & interfaces.

[29]  Wenhai Huang,et al.  Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model. , 2015, Biomaterials.

[30]  Yufeng Zheng,et al.  Noninvasive rapid bacteria-killing and acceleration of wound healing through photothermal/photodynamic/copper ion synergistic action of a hybrid hydrogel. , 2018, Biomaterials science.

[31]  D. Stout,et al.  Antibacterial properties and toxicity from metallic nanomaterials , 2017, International journal of nanomedicine.

[32]  W. Arap,et al.  A multifunctional streptococcal collagen-mimetic protein coating prevents bacterial adhesion and promotes osteoid formation on titanium. , 2014, Acta biomaterialia.

[33]  Mahendra Rai,et al.  Bioactivity, mechanism of action, and cytotoxicity of copper-based nanoparticles: A review , 2013, Applied Microbiology and Biotechnology.

[34]  Xinge Zhang,et al.  Single Continuous Near-Infrared Laser-Triggered Photodynamic and Photothermal Ablation of Antibiotic-Resistant Bacteria Using Effective Targeted Copper Sulfide Nanoclusters. , 2017, ACS applied materials & interfaces.

[35]  R. Darouiche,et al.  Treatment of infections associated with surgical implants. , 2004, The New England journal of medicine.

[36]  Carla Renata Arciola,et al.  Implant infections: adhesion, biofilm formation and immune evasion , 2018, Nature Reviews Microbiology.

[37]  A. Johnson,et al.  The economic impact of periprosthetic infections following total knee arthroplasty at a specialized tertiary-care center. , 2014, The Journal of arthroplasty.

[38]  J. Zhang,et al.  Concentration-dependent osteogenic and angiogenic biological performances of calcium phosphate cement modified with copper ions. , 2019, Materials science & engineering. C, Materials for biological applications.

[39]  K. Neoh,et al.  Antibacterial and mechanical properties of bone cement impregnated with chitosan nanoparticles. , 2006, Biomaterials.

[40]  Je-Won Ko,et al.  Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats , 2016, International journal of nanomedicine.

[41]  K. Malizos,et al.  The socioeconomic impact of musculoskeletal infections. , 2010, The Journal of bone and joint surgery. American volume.

[42]  Wei Chen,et al.  Exploration of Graphitic-C3N4 Quantum Dots for Microwave-Induced Photodynamic Therapy. , 2017, ACS biomaterials science & engineering.

[43]  Junyang Zhuang,et al.  Strong Near-Infrared Absorbing and Biocompatible CuS Nanoparticles for Rapid and Efficient Photothermal Ablation of Gram-Positive and -Negative Bacteria. , 2017, ACS applied materials & interfaces.

[44]  Michael J. MacCoss,et al.  Aminoglycoside antibiotics induce bacterial biofilm formation , 2005, Nature.

[45]  Zhenkun Zhang,et al.  Surface-Adaptive, Antimicrobially Loaded, Micellar Nanocarriers with Enhanced Penetration and Killing Efficiency in Staphylococcal Biofilms. , 2016, ACS nano.

[46]  R. Aminov,et al.  The role of antibiotics and antibiotic resistance in nature. , 2009, Environmental microbiology.

[47]  C. Wilhelm,et al.  Iron Oxide Nanoflowers @ CuS Hybrids for Cancer Tri-Therapy: Interplay of Photothermal Therapy, Magnetic Hyperthermia and Photodynamic Therapy , 2019, Theranostics.

[48]  F. Huang,et al.  The disruption of bacterial membrane integrity through ROS generation induced by nanohybrids of silver and clay. , 2009, Biomaterials.

[49]  Siddhartha P Duttagupta,et al.  Strain specificity in antimicrobial activity of silver and copper nanoparticles. , 2008, Acta biomaterialia.

[50]  Adam J Friedman,et al.  Nanotechnology as a therapeutic tool to combat microbial resistance. , 2013, Advanced drug delivery reviews.

[51]  M. Peng,et al.  Enhancing Osteosarcoma Killing and CT Imaging Using Ultrahigh Drug Loading and NIR‐Responsive Bismuth Sulfide@Mesoporous Silica Nanoparticles , 2018, Advanced healthcare materials.

[52]  P. Messersmith,et al.  Bacterial killing by light-triggered release of silver from biomimetic metal nanorods. , 2014, Small.