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The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria. Phage K, active against multiple strains of Staphylococcus aureus, including methicillin-resistant S. aureus(MRSA), was assembled with cationic poly(oxanorbornene) polymers into PPNs. The PPNs retained phage infectivity, while demonstrating enhanced biofilm penetration and killing relative to free phages. PPNs achieved 3-log10bacterial reduction (∼99.9%) against MRSA biofilms in vitro.PPNs were then incorporated into Poloxamer 407 (P407) hydrogels and applied onto in vivowound biofilms, demonstrating controlled and sustained release. Hydrogel-incorporated PPNs were effective in a murine MRSA wound biofilm model, showing a 1.5-log10reduction in bacterial load compared to a 0.5 log reduction with phage K in P407 hydrogel. Overall, this work showcases the therapeutic potential of phage K engineered with cationic polymers for treating wound biofilm infections.

Biofilms, intricate microbial communities entrenched in extracellular polymeric substance (EPS) matrices, pose formidable challenges in infectious disease treatment, especially in the context of interkingdom biofilms prevalent in the oral environment. This study investigates the potential of carvacrol-loaded biodegradable nanoemulsions (NEs) with systematically varied surface charges─cationic guanidinium (GMT-NE) and anionic carboxylate (CMT-NE). Zeta potentials of +25 mV (GMT-NE) and −33 mV (CMT-NE) underscore successful nanoemulsion fabrication (∼250 nm). Fluorescent labeling and dynamic tracking across three dimensions expose GMT-NE’s superior diffusion into oral biofilms, yielding a robust antimicrobial effect with 99.99% killing for both streptococcal and Candidaspecies and marked reductions in bacterial cell viability compared to CMT-NE (∼4-log reduction). Oral mucosa tissue cultures affirm the biocompatibility of both NEs with no morphological or structural changes, showcasing their potential for combating intractable biofilm infections in oral environment. This study advances our understanding of NE surface charges and their interactions within interkingdom biofilms, providing insights crucial for addressing complex infections involving bacteria and fungi in the demanding oral context.

Infections caused by multidrug-resistant (MDR) bacteria present an emerging global health crisis, and the threat is intensified by the involvement of biofilms. Some biofilm infections involve more than one species; this can further challenge treatment using traditional antibiotics. Nanomaterials are being developed as alternative therapeutics to traditional antibiotics; here we report biodegradable polymer-stabilized oil-in-water nanosponges (BNS) and show their activity against dual-species bacterial biofilms. The described engineered nanosponges demonstrated broad-spectrum antimicrobial activity through prevention of dual-species biofilm formation as well as eradication of preformed biofilms. The BNS showed no toxicity against mammalian cells. Together, these data highlight the therapeutic potential of this platform.

Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative ‘outside of the box’ therapeutics. Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance. In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections. In this Review, we highlight the general mechanisms by which nanomaterials can be used to target bacterial infections associated with acquired antibiotic resistance and biofilms. We emphasize design elements and properties of nanomaterials that can be engineered to enhance potency. Lastly, we present recent progress and remaining challenges for widespread clinical implementation of nanomaterials as antimicrobial therapeutics.

Bacterial wound infections are a threat to public health. Although antibiotics currently provide front-line treatments for bacterial infections, the development of drug resistance coupled with the defenses provided through biofilm formation render these infections difficult, if not impossible, to cure. Antimicrobials from natural resources provide unique antimicrobial mechanisms and are generally recognized as safe and sustainable. Herein, an all-natural antimicrobial platform is reported. It is active against bacterial biofilms and accelerates healing of wound biofilm infections in vivo. This antimicrobial platform uses gelatin stabilized by photocrosslinking using riboflavin (vitamin B2) as a photocatalyst, and carvacrol (the primary constituent of oregano oil) as the active antimicrobial. The engineered nanoemulsions demonstrate broad-spectrum antimicrobial activity towards drug-resistant bacterial biofilms and significantly expedite wound healing in an in vivomurine wound biofilm model. The antimicrobial activity, wound healing promotion, and biosafety of these nanoemulsions provide a readily translatable and sustainable strategy for managing wound infections.

Bioorthogonal catalysis offers a unique strategy to modulate biological processes through the in situ generation of therapeutic agents. However, the direct application of bioorthogonal transition metal catalysts (TMCs) in complex media poses numerous challenges due to issues of limited biocompatibility, poor water solubility, and catalyst deactivation in biological environments. We report here the creation of catalytic “polyzymes”, comprised of self-assembled polymer nanoparticles engineered to encapsulate lipophilic TMCs. The incorporation of catalysts into these nanoparticle scaffolds creates water-soluble constructs that provide a protective environment for the catalyst. The potential therapeutic utility of these nanozymes was demonstrated through antimicrobial studies in which a cationic nanozyme was able to penetrate into biofilms and eradicate embedded bacteria through the bioorthogonal activation of a pro-antibiotic.

Infections caused by bacterial biofilms are challenging to diagnose because of the complexity of both the bacteria and the heterogeneous biofilm matrix. We report here a robust polymer-based sensor array that uses selective interactions between polymer sensor elements and the biofilm matrix to identify bacteria species. In this array, an appropriate choice of fluorophore enabled excimer formation and interpolymer FRET, generating six output channels from three polymers. Selective multivalent interactions of these polymers with the biofilm matrices caused differential changes in fluorescent patterns, providing a species-based signature of the biofilm. The real-world potential of the platform was further validated through identification of mixed-species bacterial biofilms and discrimination of biofilms in a mammalian cell-biofilm co-culture wound model.

Magnetic nanoparticles are important tools for biomedicine, where they serve as versatile multifunctional instruments for a wide range of applications. Among these applications, magnetic hyperthermia is of special interest for the destruction of tumors and triggering of drug delivery. However, many applications of magnetic nanoparticles require high-quality magnetic nanoparticles displaying high specific absorption rates (SARs), which remains a challenge today. We report here the functionalization and stabilization in aqueous media of highly magnetic 15 nm iron carbide nanoparticles featuring excellent heating power through magnetic induction. The challenge of achieving water solubility and colloidal stability was addressed by designing and using specific dopamine-based ligands. The resulting nanoparticles were completely stable for several months in water, phosphate, phosphate-buffered saline, and serum-containing media. Iron carbide nanoparticles displayed high SARs in water and viscous media (water/glycerol mixtures), even after extended exposition to water and oxygen (SAR up to 1000 W·g–1in water at 100 kHz, 47 mT). The cytotoxicity and cellular uptake of iron carbide nanoparticles could be easily tuned and were highly dependent on the chemical structure of the ligands used.

The rapid emergence of antibiotic-resistant bacterial “superbugs” with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semirigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of polymeric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial resistance toward these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant antibiotics where significant resistance occurred after only a few passages.

A glycan‐stimulated and poly(3,4‐ethylene‐dioxythiophene)s (PEDOT)‐based nanomaterial platform is fabricated to purify circulating tumor cells (CTCs) from blood samples of prostate cancer (PCa) patients. This new platform, phenylboronic acid (PBA)‐grafted PEDOT NanoVelcro, combines the 3D PEDOT nanosubstrate, which greatly enhances CTC capturing efficiency, with a poly(EDOT‐PBA‐co‐EDOT‐EG3) interfacial layer, which not only provides high specificity for CTC capture upon antibody conjugation but also enables competitive binding of sorbitol to gently release the captured cells. CTCs purified by this PEDOT NanoVelcro chip provide well‐preserved RNA transcripts for the analysis of the expression level of several PCa‐specific RNA biomarkers, which may provide clinical insights into the disease. A glycan‐stimulated and poly(3,4‐ethylene‐dioxythiophene) (PEDOT)‐based nanomaterial platformis fabricated to purify circulating tumor cells. This PEDOT NanoVelcro chip not only provides highly efficient and specific capture of cancer cells but also enables competitive binding of glycan with higher affinity (i.e., sorbitol) to release them. Cancer cells purified are further utilized to correlate disease‐related RNA biomarkers in prostate cancer patients.

In article number 1700701, Hsiao‐hua Yu and co‐workers purified circulating tumor cells (CTCs) from blood samples of prostate cancer (PCa) patients. This platform not only captures CTCs with high efficiency and specificity, but also, released these cells gently by a competitive‐binding mechanism. The purified CTCs provide well‐preserved RNA transcripts for the analysis of the expression level of several PCa‐specific RNA biomarkers, which could provide clinical insights into the disease and valuable information for cancer diagnosis and therapeutics.