ROS Turn Nanoparticle Fluorescence on for Imaging Staphylococcus aureus Infection In Vivo

Abstract

Direct, noninvasive, and real‐time imaging of Staphylococcus aureus (S. aureus) infection is of great value for quick diagnosis of related disease in clinic, but remains challenging. Herein, employing a rationally designed near‐infrared fluorescence probe Cys(StB u)‐EDA‐Thioketal‐Lys(Cy5.5)‐CBT (TK‐CBT) and a CBT‐Cys click reaction, the fluorescence‐quenched nanoparticles TK‐CBT‐NPs are facilely prepared. Upon oxidation by the abundant reactive oxygen species in S. aureus‐infected macrophages, TK‐CBT‐NPs are fractured, turning the fluorescence “on” for imaging infections in vitro and in vivo. Specifically, TK‐CBT‐NPs show a 6.1‐fold fluorescence imaging signal enhancement of the macrophages that are infected by S. aureus for 20 h in vitro. At 4 h postinjection, TK‐CBT‐NPs show a 2.8‐fold fluorescence imaging signal enhancement of the sites in mice that are infected by S. aureus for 24 h. It is anticipated that TK‐CBT‐NPs could be applied for diagnosis of S. aureus infections in clinic in the near future.

Stimulus‐Responsive Amino Acids Behind In Situ Assembled Bioactive Peptide Materials

“…[68,112] In addition, establishment of the intimate relationship between the bioactivity of the materials and the assembling process enables to further optimize material performance. [113] For instance, when utilizing peptide assemblies as platforms for theranostic agents, while the fluorescence signals from probes could be enhanced by the formed assemblies, [114] accumulation and retention of drugs at tumor sites are improvable following formation of peptide assemblies. [115] In some specific cases, the assembling process potentially gives rise to the cooperativity between different bioactive moieties and thereby amplifying the entire bioactivity.…”

An activatable NIR‐II fluorescent probe for tracking heavy‐metal ion and high‐level salt‐induced oxidative stress in plant sprouts

“…The establishment of local ROS overproduction is usually transient as ROS has a short half-life; hence the in-situ, real-time and non-invasive detection and imaging of the ROS biomarker is optimal for accurately pinpointing the site with ROS amplification and accumulation. [13][14][15][16] Fluorescence imaging is a non-invasive technique that can detect and monitor in-situ biological processes including the variation of biomarker levels in a real-time manner. [17][18][19][20][21][22][23][24][25][26][27][28][29] In particular, near-infrared second window fluorescence imaging (emission: 900-1700 nm, which is referred to as NIR-II fluorescence imaging) can realize exceptional imaging performance, [30][31][32][33][34][35][36][37][38][39][40][41] since there exists almost no interference from the plant-related pigments in the NIR-II wavelength range.…”

Granzyme B Turns Nanoparticle Fluorescence “On” for Imaging Cytotoxic T Lymphocyte Activity in Vivo

“…To date, several types of “turn-on” fluorescence probes, including peptide-based small molecular probes, macromolecular reporters, and semiconducting polymer nanoprobes have been reported for early and accurate tracking of GraB activity, as well as consequent monitoring the tumoricidal activity of CTLs. − However, their initial “off” signals were achieved through “single quenching” strategies (e.g., fluorescence resonance energy transfer (FRET), intramolecular charge transfer (ICT), , or aggregation-caused quenching (ACQ)). Recent studies showed that “dual quenched” probes simultaneously using two different quenching strategies possess higher sensitivity for protease activity detection due to their additionally reduced background signals . For example, using a 2-cyanobenzothiazole-cysteine (CBT-Cys) click condensation reaction, , our group developed a “dual quenched” probe, whose fluorescence was quenched through simultaneous intra- and intermolecular quenching, to achieve enhanced “turn-on” fluorescence to specifically image furin activity in living MDA-MB-468 cells .…”

“…To prepare the nanoparticles, we rationally designed a “smart” small molecular fluorescence probe, Cys­(StBu)-Ile-Glu-Phe-Asp-Lys­(Cy5.5)-CBT ( Cy5.5-CBT ), as illustrated in Figure . After the reduction of its disulfide bond, the probe Cy5.5-CBT exposed its 1,2-aminothiol group to click condense with CBT moiety of another Cy5.5-CBT to form the cyclic dimeric product Cy5.5-CBT-Dimer , which spontaneously self-assembled into Cy5.5-CBT-NPs with a “dual quenched” fluorescence signal through intermolecular hydrophobic interaction and π–π stacking. ,− After being endocytosed by tumor cells, Cy5.5-CBT-NPs were subjected to GraB cleavage, and the nanoparticles were disassembled, turning the fluorescence “on”. As the enzymatic activity of GraB is directly related to the tumoricidal activity of CTLs and immune-mediated tumor cell killing enhancements, Cy5.5-CBT-NPs could behave as direct reporters of CTL activity in B16-OVA tumors of living mice during their cancer immunotherapy.…”

“…Recent studies showed that "dual quenched" probes simultaneously using two different quenching strategies possess higher sensitivity for protease activity detection due to their additionally reduced background signals. 36 For example, using a 2-cyanobenzothiazole-cysteine (CBT-Cys) click condensation reaction, 37,38 our group developed a "dual quenched" probe, whose fluorescence was quenched through simultaneous intra-and intermolecular quenching, to achieve enhanced "turn-on" fluorescence to specifically image furin activity in living MDA-MB-468 cells. 39 However, to the best of our knowledge, such fluorescence "dual quenched" nanoparticles have not been utilized to monitor CTL activity.…”