Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on Staphylococcus aureus (S. aureus) bacteria and through in vivo screening in mice with S. aureus-induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in S. aureus-infected tissues and reduces the needed overall systemic dose, minimizing side effects. CARG binds specifically to S. aureus bacteria but not Pseudomonas bacteria in vitro, selectively accumulates in S. aureus-infected lungs and skin of mice but not in non-infected tissue and Pseudomonas-infected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing the peptide in S. aureus-infected mouse lung tissue. The targeted nanoparticles more effectively suppress staphylococcal infections in vivo relative to equivalent doses of untargeted vancomycin nanoparticles or of free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles bearing peptides targeting infected tissue may help combat difficult-to-treat infections.

Coumarins fused with other aromatic units have recently emerged as a hot topic of research. Their synthesis is partly based on classical methodologies such as Pechmann reaction or Knoevenagel condensation, but it also sparked the discovery of completely new pathways. In very recent years so-called vertically-expanded coumarins were synthesized, effectively expanding the portfolio of existing architectures. A subtle relationship exists between the structure of fused coumarins and their optical properties. Although absorption of UV-radiation and light is unifying theme among these π-expanded coumarins, the fluorescence properties strongly depend on the structure. The mode of fusion, the type of additional ring and the presence of electron-donating and electron-withdrawing substituents all influence the photophysical parameters. Recent advances made it possible to modulate their absorption from 300 nm to 550 nm, resulting in new coumarins emitting orange light. This review serves as a guide through both synthesis strategies and structure-property relationship nuances. Strong intramolecular charge-transfer character made it possible to reach suitable values of two-photon absorption crosssection. Photophysical advantages of π-expanded coumarins have been already utilized in fluorescence probes and two-photon excited fluorescence microscopy.

Fluorescence imaging of tissues offer an essential means for studying biological systems. Autofluorescence becomes a serious issue in tissue imaging under excitation at UV-vis wavelengths where biological molecules compete with the fluorophore. To address this critical issue, a novel class of fluorophores that can be excited at ∼900 nm under two-photon excitation conditions and emits in the red wavelength region (≥600 nm) has been disclosed. The new π-extended dipolar dye system shows several advantageous features including minimal autofluorescence in tissue imaging and pronounced solvent-sensitive emission behavior, compared with a widely used two-photon absorbing dye, acedan. As an important application of the new dye system, one of the dyes was developed into a fluorescent probe for amyloid-β plaques, a key biomarker of Alzheimer's disease. The probe enabled in vivo imaging of amyloid-β plaques in a disease-model mouse, with negligible background signal. The new dye system has great potential for the development of other types of two-photon fluorescent probes and tags for imaging of tissues with minimal autofluorescence.

Fluorescent probes are essential tools for studying biological systems. The last decade has witnessed particular interest in the development of two-photon excitable probes, owing to their advantageous features in tissue imaging compared to the corresponding one-photon probes. This review summarizes various types of two-photon probes that have been applied to bioimaging, categorized by the principles in the probe design and the target analytes, which would provide a basis for the future development of novel two-photon probes for tackling important biological issues.

Structural factors governing the poor emission of dipolar dyes in aqueous media are identified, leading to new acedan derivatives with brighter fluorescence and enhanced two-photon properties.

Besides the noble physical appearance of gold and silver, their novel chemical properties attracted the modern technology for various industrial, chemical and biological uses including medical applications. The widespread use of gold and silver, however, can cause potential hazards to our environment. Therefore, suitable detection methods are a prerequisite for the evaluation of their harmful effects as well as for studying their beneficial biological properties. Due to the several advantages over the conventional analytical methods, the fluorescence detection of gold and silver has become an active research area in recent years. In this review, we provide an overview of the reported fluorescent detection systems for gold and silver species, and discuss their sensing properties with promising features. The future scope of developments in this field of research is also mentioned.

Monoamine oxidases (MAOs) play an important role in Alzheimer’s disease (AD) pathology. We report in vivo comonitoring of MAO activity and amyloid-β (Aβ) plaques dependent on the aging of live mice with AD, using a two-photon fluorescence probe. The probe under the catalytic action of MAO produces a dipolar fluorophore that senses Aβ plaques, a general AD biomarker, enabling us to comonitor the enzyme activity and the progress of AD indicated by Aβ plaques. The results show that the progress of AD has a close correlation with MAO activity, which can be categorized into three stages: slow initiation stage up to three months, an aggressive stage, and a saturation stage from nine months. Histological analysis also reveals elevation of MAO activity around Aβ plaques in aged mice. The close correlation between the MAO activity and AD progress observed by in vivo monitoring for the first time prompts us to investigate the enzyme as a potential biomarker of AD.

Photoacoustic (PA) imaging allows visualization of the physiology and pathology of tissues with good spatial resolution and relatively deep tissue penetration. The method converts near-infrared (NIR) laser excitation into thermal expansion, generating pressure transients that are detected with an acoustic transducer. Here, we find that the response of the PA contrast agent indocyanine green (ICG) can be enhanced 17-fold when it is sealed within a rigid nanoparticle. ICG encapsulated in particles composed of porous silicon (pSiNP), porous silica, or calcium silicate all show greater PA contrast relative to equivalent quantities of free ICG, with the pSiNPs showing the strongest enhancement. A liposomal formulation of ICG performs similar to free ICG, suggesting that a rigid host nanostructure is necessary to enhance ICG performance. The improved response of the nanoparticle formulations is attributed to the low thermal conductivity of the porous inorganic hosts and their ability to protect the ICG payload from photolytic and/or thermal degradation. The translational potential of ICG-loaded pSiNPs as photoacoustic probes is demonstrated via imaging of a whole mouse brain.