Pac-Man bacteria eat nanoprobes for aggregation-enhanced imaging and killing diverse microorganisms

Currently optical-based techniques for in vivo microbial population imaging are limited by low imaging depth and highly light-scattering tissue; and moreover, are generally effective against only one specific group of bacteria. Here, we introduce an innovative Pac-Man imaging and therapy strategy, in which different bacteria displayed like Pac-Man actively eat the glucose polymer (GP)-modified gold nanoparticles through ATP-binding cassette (ABC) transporter pathway, followed by laser irradiation-mediated aggregation in the bacterial cells. As a result, the aggregates display ~ 15.2-fold enhancement in photoacoustic signals and ~ 3.0-fold enhancement in antibacterial rate compared with non-aggregated counterparts. Significantly, the developed Pac-Man strategy allows ultrasensitive imaging of as low as ~ 105 colony-forming unit (CFU) of bacteria in vivo, which is around two orders of magnitude lower than most optical contrast agents. We further demonstrate Pac-Man strategy enables the detection of ~ 107 CFU bacteria residing within tumour or gut. This technique enables visualization and treatment of diverse bacteria, setting the crucial step forward the study of microbial ecosystem.

Multimodal optical contrast agents as new tools for monitoring and tuning nanoemulsion internalisation into cancer cells. From live cell imaging to in vivo imaging of tumours

Tailor-made NIR emitting dyes were designed as multimodal optical probes.

Multivariate AND-gate substrate probes as enhanced contrast agents for fluorescence-guided surgery

The greatest challenges for surgical management of cancer are precisely locating lesions and clearly defining the margins between tumors and normal tissues. This is confounded by the characteristics of the tissue where the tumor is located as well as its propensity to form irregular boundaries with healthy tissues. To address these issues, molecularly targeted optical contrast agents have been developed to define margins in real-time during surgery1,2. However, selectivity of a contrast agent is often limited by expression of a target enzyme or receptor in both tumor and healthy tissues. Here we introduce a concept of multivariate ‘AND-gate’ optical imaging probes that require sequential processing by multiple tumor-specific enzymes to produce a fluorescent signal. This results in dramatically improved specificity as well as overall enhanced sensitivity. This general approach has the potential to be broadly applied to selectively target complex patterns of enzyme activities in diverse disease tissues for detection, treatment and therapy response monitoring.

Green synthesis of multimodal ‘OFF–ON’ activatable MRI/optical probes

We report a simple and green protocol for the preparation of redox responsive multimodal MRI/optical contrast agents based on Mn nanosheets and carbon dots.

Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging

Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR) was 1.4-fold higher compared to EC17 within 60 minutes (p<0.001). Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48–5.43). Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR) dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes.

Recent advances in Gd-chelate based bimodal optical/MRI contrast agents

Recent developments in the field of bimodal MRI/optical contrast agents, based on Gd3+-chelates are presented.

Optical Scattering Properties of Intralipid Phantom in Presence of Encapsulated Microbubbles

In imaging, contrast agents are utilized to enhance sensitivity and specificity of diagnostic modalities. In ultrasound imaging, microbubbles (MBs)—a gas-core shell-encapsulated agent—are used clinically as contrast agents. The working hypothesis of this study is that microbubbles can be employed as an intravascular contrast agent in optical imaging systems. In this work, the interaction of light and microbubbles in a turbid medium (intralipid) was investigated, particularly, the effect of MBs on the reduced scattering and absorption coefficients. Diffuse reflectance (DR) and total transmittance (TT) measurements of highly scattering intralipid suspension (0.5–5%) were measured using spectroscopic integrating sphere system in the absence and presence of Definity microbubbles. The optical properties were computed using the inverse adding doubling (IAD) software. The presence of microbubbles increased DR and decreased TT of intralipid phantoms. In the presence of MBs (0.5% volume concentration), the reflectance of the intralipid phantom increased from 35% to 100%. The reduced scattering coefficient increased significantly (30%) indicating potential use of MBs as optical contrast agents in light based modalities.