Bacterial biofilms are highly antibiotic resistant microbial cell associations that lead to chronic infections. Unlike free-floating planktonic bacterial cells, the biofilms are encapsulated in a hardly penetrable extracellular polymeric matrix and, thus, demand innovative approaches for treatment. Recent advancements on the development of gel-nanocomposite systems with tailored therapeutic properties provide promising routes to develop novel antimicrobial agents that can be designed to disrupt and completely eradicate preformed biofilms. In our study, we developed a unique thermoresponsive magnetic glycol chitin-based nanocomposite containing d-amino acids and iron oxide nanoparticles, which can be delivered and undergoes transformation from a solution to a gel state at physiological temperature for sustained release of d-amino acids and magnetic field actuated thermal treatment of targeted infection sites. The d-amino acids in the hydrogel nanocomposite have been previously reported to inhibit biofilm formation and also disrupt existing biofilms. In addition, loading the hydrogel nanocomposite with magnetic nanoparticles allows for combination thermal treatment following magnetic field (magnetic hyperthermia) stimulation. Using this novel two-step approach to utilize an externally actuated gel-nanocomposite system for thermal treatment, following initial disruption with d-amino acids, we were able to demonstrate in vitro the total eradication of Staphylococcus aureus biofilms, which were resistant to conventional antibiotics and were not completely eradicated by separate d-amino acid or magnetic hyperthermia treatments.

Multifunctional imaging nanoprobes continue to garner strong interest for their great potential in the detection and monitoring of cancer. In this study, we investigate a series of spatially arranged iron oxide nanocube-based clusters (i.e., chain-like dimer/trimer, centrosymmetric clusters, and enzymatically cleavable two-dimensional clusters) as magnetic particle imaging and magnetic resonance imaging probes. Our findings demonstrate that the short nanocube chain assemblies exhibit remarkable magnetic particle imaging signal enhancement with respect to the individually dispersed or the centrosymmetric cluster analogues. This result can be attributed to the beneficial uniaxial magnetic dipolar coupling occurring in the chain-like nanocube assembly. Moreover, we could effectively synthesize enzymatically cleavable two-dimensional nanocube clusters, which upon exposure to a lytic enzyme, exhibit a progressive increase in magnetic particle imaging signal at well-defined incubation time points. The increase in magnetic particle imaging signal can be used to trace the disassembly of the large planar clusters into smaller nanocube chains by enzymatic polymer degradation. These studies demonstrate that chain-like assemblies of iron oxide nanocubes offer the best spatial arrangement to improve magnetic particle imaging signals. In addition, the nanocube clusters synthesized in this study also show remarkable transverse magnetic resonance imaging relaxation signals. These nanoprobes, previously showcased for their outstanding heat performance in magnetic hyperthermia applications, have great potential as dual imaging probes and could be employed to improve the tumor thermo-therapeutic efficacy, while offering a readable magnetic signal for image mapping of material disassemblies at tumor sites.

Bacterial biofilms associated with orthopedic implants are notorious cell associations of pathogens that show resistance against antibiotic medications and the host immune response. The presence of hard-to-penetrate extracellular polymeric substances in the biofilm provides a protective shield against the different modes of action of conventional antimicrobial agents. To address the severe complications associated with biofilm-related infections in medical implants such as prosthetic joint infections (PJIs), we have developed a treatment approach that is based on a thermoresponsive hydrogel nanocomposite system, containing Damino acids (D-AAs) and engineered gold nanorods (AuNRs), which can undergo sol-to-gel transformation at physiological temperatures for site-specific sustained drug release. Our two-step approach that utilizes a light-actuated AuNR hydrogel composite system for a combination of photothermal treatment (PTT), following initial biofilm disruption with D-AAs, is filling a current gap to develop alternative therapies that have the potential to advance a whole range of PJI medical treatment technologies. Using this two-step approach, we were able to successfully demonstrate in vitro the effective disruption and total eradication of Staphylococcus aureus biofilms formed on different metal alloys (Ti-based, CoCr, and Ta-based alloys) used in the manufacture of prosthetic joints. Moreover, this nanocomposite treatment is safe, does not lead to thermal damage of the surrounding soft tissues, and is localized to the disruption of the biofilms on the surface of the metal alloys. This treatment modality, when adapted to an open surgical approach that is compatible to current irrigation and debridement (I&D) medical procedures, has great potential to combat chronic PJIs and may help to preserve the implant, thereby decreasing the morbidity and mortality of the alternative revision surgery procedures.

Magnetic particle spectrometry offers a reliable and facile approach for the screening of promising nanoengineered fertilizers.