The chronic infections by pathogenic Pseudomonas aeruginosa (P. aeruginosa) remain to be properly addressed. In particular, for drug‐resistant strains, limited medication is available. An in vivo pneumonia model induced by a clinically isolated aminoglycoside resistant strain of P. aeruginosa is developed. Tobramycin clinically treating P. aeruginosa infections is found to be ineffective to inhibit or eliminate this drug‐resistant strain. Here, a newly developed non‐antibiotics based nanoformulation plus near‐infrared (NIR) photothermal treatment shows a remarkable antibacterial efficacy in treating this drug‐resistant pneumonia. The novel formulation contains 50–100 nm long nanorods decorated with two types of glycomimetic polymers to specifically block bacterial LecA and LecB lectins, respectively, which are essential for bacterial biofilm development. Such a 3D display of heteromultivalent glycomimetics on a large scale is inspired by the natural strengthening mechanism for the carbohydrate–lectin interaction that occurs when bacteria initially infects the host. This novel formulation shows the most efficient bacteria inhabitation and killing against P. aeruginosa infection, through lectin blocking and the near‐infrared‐light‐induced photothermal effect of gold nanorods, respectively. Collectively, the novel biomimetic design combined with the photothermal killing capability is expected to be an alternative treatment strategy against the ever‐threatening drug‐resistant infectious diseases when known antibiotics have failed.

Biofilm is closely related to chronic infections and is difficult to eradicate. Development of effective therapy strategies to control biofilm infection is still challenging. Aiming at biofilm architecture, we designed and prepared near-infrared-activated thermosensitive liposomes with photothermal and antibiotic synergistic therapy capacity to eliminate Pseudomonas aeruginosa biofilm. The liposomes with positive charge and small size aided to enter the biofilm microchannels and locally released antibiotics in infection site. The liposomes could remain stable at 37 °C and release about 80% antibiotics over 45 °C. The biofilm dispersion rate was up to 80%, which was a 7- to 8-fold rise compared to excess antibiotic alone, indicating that the localized antibiotic release and photothermal co-therapy improved the antimicrobial efficiency. In vivo drug-loaded liposomes in treating P. aeruginosa-induced abscess exhibited an outstanding therapeutic effect. Furthermore, photothermal treatment could stimulate the expression of bcl2-associated athanogene 3 to prevent normal tissue from thermal damage. The near-infrared-activated nanoparticle carriers had the tremendous therapeutic potential to dramatically enhance the efficacy of antibiotics through thermos-triggered drug release and photothermal therapy.

The emergence of antibiotic-resistant bacterial strains has made conventional antibiotic therapies less efficient. The development of a novel nanoantibiotic approach for efficiently ablating such bacterial infections is becoming crucial. Herein, a collection of poly(5-(2-ethyl acrylate)-4-methylthiazole-g-butyl)/copper sulfide nanoclusters (PATA-C4@CuS) was synthesized for efficient capture and effective ablation of levofloxacin-resistant Gram-negative and Gram-positive bacteria upon tissue-penetrable near-infrared (NIR) laser irradiation. In this work, we took advantage of the excellent photothermal and photodynamic properties of copper sulfide nanoparticles (CuSNPs) upon NIR laser irradiation and thiazole derivative as a membrane-targeting cationic ligand toward bacteria. The conjugated nanoclusters could anchor the bacteria to trigger the bacterial aggregation quickly and efficiently kill them. These conjugated nanoclusters could significantly inhibit levofloxacin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus amyloliquefaciens at 5.5 μg/mL under NIR laser irradiation (980 nm, 1.5 W cm, 5 min), which suggested that the heat and reactive oxygen species (ROS) generated from the irradiated CuSNPs attached to bacteria were effective in eliminating and preventing the regrowth of the bacteria. Importantly, the conjugated nanoclusters could promote healing in bacteria-infected rat wounds without nonspecific damage to normal tissue. These findings highlight the promise of the highly versatile multifunctional nanoantibiotics in bacterial infection.

Biofilms' tolerance has become a serious clinical concern due to their formidable resistance to conventional antibiotics and prevalent virulence. Therefore, there is an urgent need to develop alternative antimicrobial agents to eradicate biofilms but avoid using antibiotics. Herein, we successfully developed polymer functional silver nanocomposites by reduction of silver nitrate in the presence of a biocompatible carbohydrate polymer and a membrane-disrupting cationic polymer. The nanocomposites presented effective antimicrobial activity against Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus and Bacillus amyloliquefaciens). Confocal laser scanning macroscopy imaging demonstrated that the nanocomposites could efficiently disperse and eradicate the mature biofilms formed by the above four bacterial strains. The introduction of carbohydrate polymers onto nanocomposites effectively improved the biocompatibility, and these nanocomposites induced no significant red blood cell hemolysis and cytotoxicity toward mammalian cells. More importantly, the nanocomposites were able to well eradicate the bacterial biofilms formed on the silicone implants in vivo. In conclusion, the nanocomposites as the broad-spectrum biofilm-disrupting agent are significant in the design of new strategies to eradicate biofilms on indwelling medical devices.

The chronic infection of humans by antibiotic-resistant bacteria and their related biofilm have, so far, not been properly addressed. In the present work, we developed a novel antibacterial nanoplatform showing the most efficient antibiotic-resistant bacteria inhibition and biofilm eradication. This particular formulation contains tobramycin-conjugated graphene oxide, for efficiently capturing bacteria through electrostatic interactions and eliminating bacteria as a "nano-knife", and copper sulphide nanoparticles for enhancing the photothermal and photodynamic properties. This novel formulation can selectively eliminate bacteria over NIH 3T3 cells, and the biofilm eradication capacity was up to 70%. Importantly, the nanoplatforms can inhibit bacterial growth and promote the repair of antibiotic-resistant bacteria-infected wounds on rats without non-specific damage to normal tissue. This work provides an effective, simple, and rapid method for the design and fabrication of near-infrared light-induced nanoplatforms that offer possibilities to treat biofilm-related infections.