Pancreatic β cells are responsible for insulin secretion and are important for glucose regulation in a healthy body and diabetic disease patient without prelabeling of islets. While the conventional biomarkers for diabetes have been glucose and insulin concentrations in the blood, the direct determination of the pancreatic β cell mass would provide critical information for the disease status and progression. By combining fluorination and diversity-oriented fluorescence library strategy, we have developed a multimodal pancreatic β cell probe PiF for both fluorescence and for PET (positron emission tomography). By simple tail vein injection, PiF stains pancreatic β cells specifically and allows intraoperative fluorescent imaging of pancreatic islets. PiF-injected pancreatic tissue even facilitated an antibody-free islet analysis within 2 h, dramatically accelerating the day-long histological procedure without any fixing and dehydration step. Not only islets in the pancreas but also the low background of PiF in the liver allowed us to monitor the intraportal transplanted islets, which is the first in vivo visualization of transplanted human islets without a prelabeling of the islets. Finally, we could replace the built-in fluorine atom in PiF with radioactive 18F and successfully demonstrate in situ PET imaging for pancreatic islets.

While the wide-spectrum antimicrobial properties and stability of silver nanomaterials have been copiously utilized in many medical and consumer products, we found that Methicillin Resistant Staphylococcus aureus (MRSA) is less susceptible to silver in comparison to Methicillin Sensitive Staphylococcus aureus (MSSA). Pre-exposure of MRSA to sub-lethal concentrations of AgNO3 caused 2.5-fold increase in LD50 of silver suggesting an inducible resistance mechanism. Studies involving gene expression profiling and efflux pump blockers showed the induction of P-type efflux pumps (Cop A, Cop Z and Nor B) as the principle mechanism conferring silver resistance in MRSA. Chlorpromazine—an efflux pump blocker increased sensitivity of MRSA to silver. Leveraging on these observations, silver resistance in MRSA was circumvented by enhancing the bioavailability of silver by cationic functioning of silver nanoparticles or by co-delivering silver together with chlorpromazine. Atomic Force Microscopy showed that poly-ethylene imine (PEI) functionalized silver nanoparticles adhere to bacterial cells which was found to increase the bioavailability, membrane rupture and cell death. The strategy of co-delivery of AgNO3 and chlorpromazine using chitosan-functionalized wormhole silica nanoparticles caused 12 log reduction in bacterial count which was 1000 times higher than bacterial reduction by AgNO3 alone. In short, these studies showed that circumventing antimicrobial resistance in pathogenic bacteria is possible by designed silver nanotechnology.

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