Ag ions are a well-known antibacterial agent, and Ag nanoparticles act as a reservoir of these Ag ions for targeted therapy of bacterial infections. However, there are no tools to effectively trigger and monitor the release of Ag ions from Ag nanoparticles. Photoacoustic (PA) imaging is an emerging noninvasive imaging tool, and gold nanorods (AuNRs) are an excellent contrast agent for PA imaging. In this work, we developed Au/Ag hybrid nanoparticles by coating AuNRs with silver (Ag), which decreased their photoacoustic signal. The as-prepared, Ag-coated Au nanorods (Au/AgNRs) are stable under ambient conditions, but the addition of ferricyanide solution (1 mM) results in oxidative etching of the silver shell. The PA contrast is simultaneously recovered as the silver is released, and this PA signal offers noninvasive monitoring of localized release of Ag ions. The released Ag ions exhibit a strong bactericidal efficacy similar to equivalent free Ag ions (AgNO), and the nanoparticles killed >99.99% of both (Gram-positive) methicillin-resistant Staphylococcus aureus (MRSA, 32 μM Ag equivalent) and (Gram-negative) Escherichia coli (8 μM Ag equivalent). The theranostic potential of these nanoparticles was demonstrated in a pilot in vivo study. Mice were inoculated with MRSA and Au/AgNRs were subcutaneously implanted followed by silver etching. There was a 730% increase in the PA signal ( p < 0.01) pre- and post-etching, and the bacterial counts in infected tissues of the treated group were reduced by 1000-fold (log CFU/g = 4.15 vs 7.75) versus the untreated control; this treatment efficacy was confirmed with histology. We further showed that these hybrid nanoparticles could release Ag after stimulation by reactive oxygen species including hydrogen peroxide and peroxynitrite. These hybrid Au/Ag nanoparticles are a useful theranostic agent for the photoacoustic imaging and treatment of bacterial infections.

Acoustic imaging is affordable and accessible without ionizing radiation. Photoacoustic imaging increases the contrast of traditional ultrasound and can offer good spatial resolution when used at high frequencies with excellent temporal resolution. Prussian blue nanoparticles (PBNPs) are an emerging photoacoustic contrast agent with strong optical absorption in the near-infrared region. In this study, we developed a simple and efficient method to label human mesenchymal stem cells (hMSCs) with PBNPs and imaged them with photoacoustic imaging. First, PBNPs were synthesized by the reaction of FeCl3 with K4[Fe(CN)6] in the presence of citric acid and complexed with the cationic transfection agent poly-l-lysine (PLL). The PLL-coated PBNPs (PB-PLL nanocomplexes) have a maximum absorption peak at 715 nm and could efficiently label hMSCs. Cellular uptake of these nanocomplexes was studied using bright field, fluorescence, and transmission electron microscopy. The labeled stem cells were successfully differentiated into two downstream lineages of adipocytes and osteocytes, and they showed positive expression for surface markers of CD73, CD90, and CD105. No changes in viability or proliferation of the labeled cells were observed, and the secretome cytokine analysis indicated that the expression levels of 12 different proteins were not dysregulated by PBNP labeling. The optical properties of PBNPs were preserved postlabeling, suitable for the sensitive and quantitative detection of implanted cells. Labeled hMSCs exhibited strong photoacoustic contrast in vitro and in vivo when imaged at 730 nm, and the detection limit was 200 cells/µL in vivo. The photoacoustic signal increased as a function of cell concentration, indicating that the number of labeled cells can be quantified during and after cell transplantations. In hybrid ultrasound/photoacoustic imaging, this approach offers real-time and image-guided cellular injection even through an intact skull for brain intraparenchymal injections. Our labeling and imaging technique allowed the detection and monitoring of 5 × 104 mesenchymal stem cells in living mice over a period of 14 days.

Developing in vivo cell tracking is an important prerequisite for further development of cell-based therapy. So far, few computed tomography (CT) cell tracking studies have been described due to its notoriously low sensitivity and lack of efficient labeling protocols. We present a simple method to render human mesenchymal stem cells (hMSCs) sufficiently radiopaque by complexing 40 nm citrate-stabilized gold nanoparticles (AuNPs) with poly-L-lysine (PLL) and rhodamine B isothiocyanate (RITC). AuNP-PLL-RITC labeling did not affect cellular viability, proliferation, or downstream cell differentiation into adipocytes and osteocytes. Labeled hMSCs could be clearly visualized in vitro and in vivo with a micro-CT scanner, with a detection limit of approximately 2×104 cells/μl in vivo. Calculated HU values were 2.27 /pg of intracellular Au as measured with inductively coupled plasma mass spectrophotometry (ICP-MS), and were linear over a wide range of cell concentrations. This linear CT attenuation was observed for both naked AuNPs and those that were taken up by hMSCs, indicating that the number of labeled cells can be quantified similar to the use of radioactive or fluorine tracers. This approach for CT cell tracking may find applications in CT image-guided interventions and fluoroscopic procedures commonly used for the injection of cellular therapeutics.

During the last decade, various functional nanostructured materials with interesting optical, magnetic, mechanical and chemical properties have been extensively applied to biomedical areas including imaging, diagnosis and therapy. In therapeutics, most research has focused on the application of nanoparticles as potential delivery vehicles for drugs and genes, because nanoparticles in the size range of 2-100 nm can interact with biological systems at the molecular level, and allow targeted delivery and passage through biological barriers. Recent investigations have even revealed that several kinds of nanomaterials are intrinsically therapeutic. Not only can they passively interact with cells, but they can also actively mediate molecular processes to regulate cell functions. This can be seen in the treatment of cancer via anti-angiogenic mechanisms as well as the treatment of neurodegenerative diseases by effectively controlling oxidative stress. This review will present recent applications of inorganic nanoparticles as therapeutic agents in the treatment of disease.

Stem cell therapy has the potential to improve tissue remodeling and repair. For cardiac stem cell therapy, methods to improve the injection and tracking of stem cells may help to increase patient outcomes. Here we describe a multimodal approach that combines ultrasound imaging, photoacoustic imaging, and magnetic particle imaging (MPI). Ultrasound imaging offers real-time guidance, photoacoustic imaging offers enhanced contrast, and MPI offers high-contrast, deep-tissue imaging. This work was facilitated by a poly(lactic-co-glycolic acid) (PLGA)-based iron oxide nanobubble labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) as a trimodal contrast agent. The PLGA coating facilitated the ultrasound signal, the DiR increased the photoacoustic signal, and the iron oxide facilitated the MPI signal. We confirmed that cell metabolism, proliferation, differentiation, and migration were not adversely affected by cell treatment with nanobubbles. The nanobubble-labeled cells were injected intramyocardially into live mice for real-time imaging. Ultrasound imaging showed a 3.8-fold increase in the imaging intensity of labeled cells postinjection compared to the baseline; photoacoustic imaging showed a 10.2-fold increase in the cardiac tissue signal postinjection. The MPI intensity of the nanobubble-treated human mesenchymal stem cells injected into the hearts of mice was approximately 20-fold greater than the negative control.

Nanomaterials are promising tools in water remediation because of their large surface area and unique properties compared to bulky materials. We synthesized an organosilica nanoparticle (OSNP) and tuned its composition for anionic dye removal. The adsorption mechanisms are electrostatic attraction and hydrogen bonding between the amine on OSNP and the dye, and the surface charge of the OSNP can be tuned to adsorb either anionic or cationic dyes. Using phenol red as a model dye, we studied the effect of the amine group, pH, ionic strength, time, dye concentration, and nanomaterial mass on the adsorption. The theoretical maximum adsorption capacity was calculated to be 175.44 mg/g (0.47 mmol/g), which is higher than 67 out of 77 reported adsorbents. The experimental maximum adsorption capacity is around 201 mg/g (0.53 mmol/g). Furthermore, the nanoparticles are highly reusable and show stable dye removal and recovery efficiency over at least 10 cycles. In summary, the novel adsorbent system derived from the intrinsic amine group within the frame of OSNP are reusable and tunable for anionic or cationic dyes with high adsorption capacity and fast adsorption. These materials may also have utility in drug delivery or as a carrier for imaging agents.

Rheumatoid arthritis (RA) is an autoimmune disease that affects 1-2% of the human population worldwide, and effective therapies with targeted delivery for local immune suppression have not been described. We address this problem by developing a novel theranostic nanoparticle for RA and assessed its therapeutic and targeting effects under image-guidance. Methods: Albumin-cerium oxide nanoparticles were synthesized by the biomineralization process and further conjugated with near-infrared, indocyanine green (ICG) dye. Enzymatic-like properties and reactive oxygen species (ROS) scavenging activities, as well as the ability to reprogram macrophages, were determined on a monocyte cell line in culture. The therapeutic effect and systemic targeting potential were evaluated in collagen-induced arthritis (CIA) mouse model using optical/optoacoustic tomographic imaging. Results: Small nanotheranostics with narrow size distribution and high colloidal stability were fabricated and displayed high ROS scavenging and enzymatic-like activity, as well as advanced efficacy in a converting pro-inflammatory macrophage phenotype into anti-inflammatory phenotype. When administrated into affected animals, these nanoparticles accumulated in inflamed joints and revealed a therapeutic effect similar to the gold-standard therapy for RA, methotrexate. Conclusions: The inflammation-targeting, inherent contrast and therapeutic activity of this new albumin-cerium oxide nanoparticle may make it a relevant agent for assessing severity in RA, and other inflammatory diseases, and controlling inflammation with image-guidance. The design of these nanotheranostics will enable potential clinical translation as systemic therapy for RA.

The present findings suggest that walking among community-dwelling older adults can be more effective for fall prevention than balance training. However, because walking can induce more trips, walking should not be recommended for older adults who are susceptible to falling or frailty.