Bioorthogonal surface-enhanced Raman scattering flower-like nanoprobe with embedded standards for accurate cancer cell imaging.

Developing precise and effective strategies for cancer identification and imaging is attractive due to their importance for early cancer detection, prognosis, and subsequent treatment. Herein, we reported a novel bioorthogonal surface-enhanced Raman scattering (SERS) nanoprobe for accurate cancer cell imaging. A novel core-molecule-shell nanoflower (Au@4-MBN@Au) with rich electromagnetic hot spots and enhanced Raman scattering was first synthesized by optimizing the embedded concentrations of 4-mercaptobenzonitrile (4-MBN). Then, Au@4-MBN@Au was further modified with FA-PEG-SH molecules to acquire the bioorthogonal SERS nanoprobe Au@4-MBN@Au-PEG-FA. The SERS nanoprobe illustrated a robust and stable nitrile stretching vibration Raman signal (2223 cm-1) in the cellular silent region, ensuring high sensitivity and ultra-accuracy SERS imaging of cancer cells. Furthermore, cell imaging results demonstrated Au@4-MBN@Au-PEG-FA could recognize FR-positive HeLa cells with high selectivity due to the high affinity between folate receptor and folic acid. More notably, Au@4-MBN@Au-PEG-FA has been applied to identify FR-positive Hela cells from co-cultured cancer cells with similar morphology by SERS imaging for the first time. With improved signal-to-background ratio, high selectivity, and excellent stability, we anticipate the SERS nanoprobe Au@4-MBN@Au-PEG-FA could be applied for FR-related cancer theranostics and clinical detection in the future.

Internal Standard Assisted Surface-Enhanced Raman Scattering Nanoprobe with 4-NTP as Recognition Unit for Ratiometric Imaging Hydrogen Sulfide in Living Cells.

Hydrogen sulfide (H2S), as the third endogenous gasotransmitter, is closely associated with various physiological and pathological processes, whereas many aspects of its functions remain unclear. Effective tools for the accurate detection of H2S in living organisms are urgently needed. We herein reported an internal standard assisted surface-enhanced Raman scattering (SERS) nanoprobe for ratiometric detection of H2S in vitro and in living cells based on the reduction of nitros with H2S. This nanoprobe consists of an internal standard (4-mercaptobenzonitrile, MPBN) embedded core-molecule-shell Au nanoflower (Au@MPBN@Au) as the high plasmonic active SERS substrate and the 4-nitrothiophenol (4-NTP) molecule immobilized on the surface as the H2S recognition unit. With the addition of H2S, the nitros peak (1329 cm-1) decreased. Meanwhile, three obvious new peaks appeared at 1139, 1387, and 1433 cm-1, which were related to the vibration of the dimerized product 4,4'-dimercaptoazobisbenzene (DMAB) of 4-aminothiophenol (4-ATP). However, the peak intensity at 2223 cm-1 derived from MPBN was not influenced by the outer environment. Thus, the H2S level was able to be determined based on the ratio of two peak intensities (I1139/I2223) with a detection limit as low as 0.24 µM. Notably, we have proved that SERS nanoprobe Au@MPBN@Au@4-NTP could ratiometrically image both the endogenous and exogenous H2S in living cells. We anticipate that Au@MPBN@Au@4-NTP could be applied for the study of H2S-related physiological function in the future.

A near-infrared fluorescent probe for ratiometric sensing of SO2 in cells and zebrafish.

Developing suitable molecular tools for monitoring SO2 and its derivatives in living organisms is attractive due to their importance for human health. Herein, the first near-infrared fluorescent probe Mito-HN with aggregation-induced emission enhancement (AIEE) characteristics for ratiometric sensing of SO2 derivatives in vitro, in cells, and in zebrafish was designed and synthesized. By connecting the electron-donating naphthopyran and electron-withdrawing hemicyanine via the alkenyl group, this probe displays a near-infrared fluorescence emission and notable solid-state luminescence with AIEE features. Based on the specific 1,4-addition reaction of HSO3-/SO32- with the C[double bond, length as m-dash]C double bond of Mito-HN, this probe can specifically sense HSO3- in real time with an excellent near-infrared ratiometric fluorescence effect, a low detection limit of 0.17 µM, and a fast response time of less than 30 s. Cell imaging and zebrafish imaging results demonstrate that Mito-HN can ratiometrically not only sense endogenous SO2 derivatives in mitochondria but also monitor SO2 in living organisms. We anticipate that Mito-HN could be applied for the diagnosis of SO2-related diseases in the future.

Unique phenolic constituent in Cimicifuga dahurica (Turcz.) Maxim. through Box-Behnken design and response surface methodology.

Cimicifuga dahurica (Turcz.) Maxim. exerts significant antioxidative due to its high phenolic constituent content. In this study, the extraction condition of the phenolic constituents and antioxidant effect was optimized by the Box-Behnken design and response surface methodology. Eleven main bioactive analytes of Cimicifuga dahurica (Turcz.) Maxim. were simultaneously quantified by high-performance capillary electrophoresis with diode-array detector to assess the effect of extraction technology. The optimal extraction parameters were determined as: the concentration of ethanol 56.21%, liquid/solid ratio 14.65:1, and extraction time 1.64 h for 2.67 times. According to the results, a maximal value of total phenolic acids (3.67 mg/g) was obtained. Meanwhile, the influence of different extraction technology on antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonate), ferric reducing antioxidant power and hydroxyl radical scavenging method. The results presented here showed that the content of phenolic acid and antioxidant effect was much higher than the European Pharmacopoeia. Altogether, this method successfully applied response surface methodology to optimize the Cimicifuga dahurica (Turcz.) Maxim. extract with high antioxidant activities.