Unique Fluorescent Imaging Probe for Bacterial Surface Localization and Resistant Enzyme Imaging.

Emergence of antibiotic bacterial resistance has caused serious clinical issues worldwide due to increasingly difficult treatment. Development of a specific approach for selective visualization of resistant bacteria will be highly significant for clinical investigations to promote timely diagnosis and treatment of bacterial infections. In this article, we present an effective method that not only is able to selectively recognize drug resistant AmpC ß-lactamases enzyme but, more importantly, is able to interact with bacterial cell wall components, resulting in a desired localization effect on the bacterial surface. A unique and specific enzyme-responsive cephalosporin probe (DFD-1) has been developed for the selective recognition of resistance bacteria AmpC ß-lactamase, by employing fluorescence resonance energy transfer with an "off-on" bioimaging. To achieve the desired localization, a lipid-azide conjugate (LA-12) was utilized to facilitate its penetration into the bacterial surface, followed by copper-free click chemistry. This enables the probe DFD-1 to be anchored onto the cell surface. In the presence of AmpC enzymes, the cephalosporin ß-lactam ring on DFD-1 will be hydrolyzed, leading to the quencher release, thus generating fluorescence for real-time resistant bacterial screening. More importantly, the bulky dibenzocyclooctyne group in DFD-1 allowed selective recognition toward the AmpC bacterial enzyme instead of its counterpart ( e.g., TEM-1 ß-lactamase). Both live cell imaging and cell cytometry assays showed the great selectivity of DFD-1 to drug resistant bacterial pathogens containing the AmpC enzyme with significant fluorescence enhancement (∼67-fold). This probe presented promising capability to selectively localize and screen for AmpC resistance bacteria, providing great promise for clinical microbiological applications.

Correction: Enzyme-responsive reporter molecules for selective localization and fluorescence imaging of pathogenic biofilms.

Correction for 'Enzyme-responsive reporter molecules for selective localization and fluorescence imaging of pathogenic biofilms' by Junxin Aw et al., Chem. Commun., 2017, 53, 3330-3333.

Nanostructures for NIR light-controlled therapies.

In general, effective clinical treatment demands precision medicine, which requires specific perturbation to disease cells with no damage to normal tissue. Thus far, guaranteeing that selective therapeutic effects occur only at targeted disease areas remains a technical challenge. Among the various endeavors to achieve such an outcome, strategies based on light-controlled therapies have received special attention, mostly due to their unique advantages, including the low-invasive property and the capability to obtain spatial and temporal precision at the targeted sites via specific wavelength light irradiation. However, most conventional light-mediated therapies, especially those based on short-wavelength UV or visible light irradiation, have potential issues including limited penetration depth and harmful photo damage to healthy tissue. Therefore, the implemention of near-infrared (NIR) light illumination, which can travel into deeper tissues without causing obvious photo-induced cytotoxcity, has been suggested as a preferable option for precise phototherapeutic applications in vitro and in vivo. In this article, an overview is presented of existing therapeutic applications through NIR light-absorbed nanostructures, such as NIR light-controlled drug delivery, NIR light-mediated photothermal and photodynamic therapies. Potential challenges and relevant future prospects are also discussed.

Enzyme-responsive reporter molecules for selective localization and fluorescence imaging of pathogenic biofilms.

Pathogenic bacteria and their biofilm formation are responsible for a broad spectrum of microbial infections. A novel enzyme-responsive reporter molecule (ERM-1), which can specifically recognize AmpC ß-lactamase (Bla) in drug resistant bacteria, has been developed to enable the selective localization of biofilms.

In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics.

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

Enzyme-responsive multifunctional magnetic nanoparticles for tumor intracellular drug delivery and imaging.

Enzyme-responsive, hybrid, magnetic silica nanoparticles have been employed for multifunctional applications in selective drug delivery and intracellular tumor imaging. In this study, doxorubicin (Dox)-conjugated, enzyme-cleavable peptide precursors were covalently tethered onto the surface of uniform silica-coated magnetic nanoparticles through click chemistry. This enzyme-responsive nanoparticle conjugate demonstrated highly efficient Dox release upon specific enzyme interactions in vitro. It also exhibits multiple functions in selective tumor intracellular drug delivery and imaging in the tumor cells with high cathepsin B expression, whereas it exhibited lower cytotoxicity towards other cells without enzyme expression.