Search

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l -Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications. Tris-assisted one-step fabrication of functional F-CDs for specific folate receptor positive-expressed cancer cell imaging. [Display omitted] • F-CDs were fabricated via rich hydroxyl groups Tris to mediate hydrothermal process of FA and L-Arg. • Rich hydroxyl groups of Tris play a vital role in the optical properties and intrinsic targeting ability for FR positive-expressed cancer cell for labeling and tracking. • This study provides an efficient strategy to design fluorescent CDs for extensive applications. [ABSTRACT FROM AUTHOR]

Fluorescent sensors have been widely applied for biosensing, but probes for both multiple analytes sensing and photodynamic therapy (PDT) effect are less reported. In this article, we reported three AIE-based probes anchored with different mass-weight polyethylene glycol (PEG) tails, i.e., TPE-PEG160 , TPE-PEG350 , and TPE-PEG750 , for both adenosine-5′-triphosphate (ATP) and hydrogen sulfide (H 2 S) detection and also cancer cells photodynamic therapy. TPE-PEGn s (n = 160, 350 and 750) contain the tetraphenylethylene-based fluorophore core, the pyridinium and amide anion binding sites, the H 2 S cleavable disulfide bond, and the hydrophilic PEG chain. They exhibit a good amphiphilic property and can self-assemble nona-aggregation with a moderated red emission in an aqueous solution. Importantly, the size of aggregation, photophysical property, sensing ability and photosensitivity of these amphiphilic probes can be controlled by tuning the PEG chain length. Moreover, the selected probe TPE-PEG160 has been successfully used to detect environmental H 2 S and image ATP levels in living cells, and TPE-PEG750 has been used for photodynamic therapy of tumor cells under light irradiation. Three novel AIE-based probes TPE-PEGn s (n = 160, 350, 750) for both ATP and H 2 S detection and also cancer cells photodynamic therapy have been reported. [Display omitted] • Three novel AIE-based probes TPE-PEGn s (n = 160, 350, 750) were prepared. • TPE-PEGn s can detect ATP and H 2 S with a high sensitivity and selectivity. • Properties (size, optics, sensing) of TPE-PEGn s can be affected by PEG chain. • TPE-PEG160 can detect environmental H 2 S and image ATP in living cells. • TPE-PEG750 has been used for image-guided killing of cancer cells. [ABSTRACT FROM AUTHOR]

Fluorogenic substrates are used to visualize the activity of cancer-associated enzymes and to interpret biological events. Certain types of glutathione S-transferase (GST), such as Pi class GST (referred to as GSTP1), are more highly expressed in a wide variety of human cancer tissues compared to their corresponding normal tissues. Pi class GST is thus a cancer cell molecular marker and potential target for overcoming resistance to chemotherapy. Here, we report that 4-bromo-1,8-naphthalimide (BrNaph) is a practical fluorogenic GST substrate. We have found that HE-BrNaph , an N -hydroxyethyl derivative, shows remarkable fluorescence enhancement upon GST-catalyzed S N Ar replacement of the bromo group with a glutathionyl group. This substitution was highly selective and occurred only in the presence of GSH/GSTs; no non-enzymatic reaction was observed. We demonstrated that HE-BrNaph allows visualization of GST activity in living cells and enables to distinguish cancer cells from normal cells. Further, various N -substitutions in BrNaph retain susceptibility to enzymatic activity and isozyme selectivity, suggesting the applicability of BrNaph derivatives. Thus, BrNaph and its derivatives are GST substrates useful for fluorescence imaging and the intracellular detection of GSTP1 activity in living cells. Image 1 • HE-BrNaph shows a large fluorescence enhancement upon catalysis by GST. • HE-BrNaph was used for live cell imaging of GSTP1 activity. • Various N -substitutions in BrNaph were tolerated by the enzymatic reaction and maintained isozyme selectivity. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world, which can lead to considerably high mortality rate. It was reported that the prognosis is extremely poor and survival is often measured in months once CRC metastases become clinically evident. Therefore, the development of effective approach for metastatic CRC cells detection and imaging may potentially be significant and helpful for CRC prognosis and treatment. Therefore, we proposed a sensitive and specific approach for high-metastatic CRC LoVo cells detection and imaging by using terminal deoxynucleotidyl transferase (TdT)-initiated molecule beacons (MBs) arrayed fluorescent aptamer probes (denoted as TMAP). In this approach, the aptamer W3 targeting high-metastatic CRC LoVo cells was elongated to form W3-poly A at the 3′-hydroxyl terminus with repeated A bases in the presence of TdT and dATP. The MBs designed with poly T sequence in the loop were then hybridized with the poly A in the aptamer W3. The TMAP was easily constructed without the need of aptamer modification. It was demonstrated that this approach could specifically detect and image the high-metastatic CRC LoVo cells from the mixture of high-metastatic CRC LoVo cells and non-metastatic HCT-8 cells. Compared with 6-carboxyfluorescein (6-FAM) labeled aptamer W3, the TMAP was demonstrated to have a much stronger fluorescence signal on the target cells, realizing a 4-fold increase in signal-to-background ratio (SBR). Determination by flow cytometry allowed for detection of as low as 23 CRC LoVo cells in 200 μL cell culture medium. The high sensitivity and the capability for using in complicate biological samples imply that this approach holds considerable potential for metastatic CRC detection and therapy. Image 1 • TMAP was developed for specific detection and imaging of metastatic CRC cells. • TMAP could identify target LoVo cells with excellent binding affinity and specificity. • TMAP could specifically distinguish between the metastatic LoVo cells and non-metastatic HCT-8 cells in mixed cells samples. [ABSTRACT FROM AUTHOR]

Two different colors of water-soluble core-shell quantum dots CdTe/CdS (green and orange red) have been synthesized and characterized in this paper. The formation of core-shell quantum dots not only improves the fluorescence quantum yield, but also reduces the biological toxicity of quantum dots, and improves the fluorescence lifetime. Two novel fluorescent bioprobes, CdTe/CdS (λ em = 545 nm)-5-Fu and Bio-CdTe/CdS (λ em = 600 nm)-TAM, have been synthesized via the interaction of these two core-shell quantum dots with anticancer drugs (5-Fu) and P-gp inhibitors (TAM), respectively. These two fluorescent probes have been simultaneously used in fluorescence imaging of human breast cancer cells MDA-MB-231/MDR. It can be observed that under the action of P-gp inhibitors distributed on the cell membrane, anticancer drugs can be retained in cancer cells. According to the color of quantum dots on the probe, the visualization results of the action of anticancer drugs and P-gp inhibitors can be obtained. This study shows that to prepare functional bioprobes using core-shell quantum dots CdTe/CdS has great potential in the field of biomedical research such as anticancer drugs. Image 1 • CdTe/CdS core-shell QDs has higher fluorescence quantum yield and lower biological toxicity. • Simultaneous imaging of two bioprobes (CdTe/CdS-5-Fu, Bio-CdTe/CdS-TAM) in cancer cells. • Surface functionalization of quantum dots by anticancer drugs 5-Fu and P-gp inhibitors TAM. • Two colors bioprobes visualize the Interaction between Anticancer Drugs and P-gp Inhibitors. [ABSTRACT FROM AUTHOR]

Abstract Anterior gradient protein 2 homolog (AGR) is a potential tumor biomarker and plays an important role in tissue development and regeneration. The intracellular detection of AGR is rarely reported. By conjugating the AGR aptamer with a cytosine base sequence as Ag cluster template, a highly fluorescent probe (MA@AgNCs) was synthesized for targeting intracellular AGR. The MA@AgNCs display a maximum fluorescence peak at 565 nm, and possess an excellent quantum yield (QY = 87.43%), small size, great biocompatibility, low toxicity, and good stability. Moreover, the as synthesized MA@AgNCs show high specificity on recognizing breast cancer cells. Graphical abstract Scheme 1 The sketch of synthesis process and fluorescence cell imaging. fx1 Highlights • The MA@AgNCs shows high quantum yield, excellent stability, and good thermostability with negligible cytotoxicity. • The MA@AgNCs imaged the AGR protein in MCF-7 cells with good selectivity between MCF-7 and Hela cells. [ABSTRACT FROM AUTHOR]

Abstract Serum albumin has a wide range of applications in biochemical experiments and pharmaceutical field. We found that a cyanine dye, dimethylindole red (Dir), could selectively interact with bovine serum albumin (BSA). Dir exhibited very weak red fluorescence, while the fluorescence intensity at 630 nm was enhanced up to 130-fold upon noncovalently interacting with 30 µM BSA. Besides, Dir showed a highly selective response to BSA over human serum albumin (HSA). For the detection of BSA, a limit of detection as low as 23 nM was obtained. Then biocompatible Dir-BSA nanoparticles were prepared by the desolvation technique. The Dir-BSA nanoparticles possess excellent fluorescence properties with a quantum yield of 32%. Furthermore, folic acid as a targeting group was conjugated to Dir-BSA nanoparticles and these nanoparticles were characterized by TEM and laser particle analyzer, etc. Folic acid-modified Dir-BSA nanoparticles were successfully used for tumor cell-targeted imaging. Graphical abstract fx1 Highlights • Dir could selectively interact with BSA compared with HSA. • The fluorescence of Dir is increased up to 130-fold upon binding to BSA. • Dir-BSA nanoparticles possess a fluorescence quantum yield of ca. 32%. • The folate modified Dir-BSA NPs could be used for targeted tumor cell imaging. [ABSTRACT FROM AUTHOR]

Early diagnosis of chronic, critical diseases improves clinical outcomes, and biomarkers play an important role as an indicator of severity or presence of a disease. Alkaline phosphatase (ALP) is one such vital biomarker in the diagnosis of several diseases. Herein we introduce a facile, sensitive fluorescent assay, based on the inner filter effect (IFE), for ALP activity determination in serum and in living cells. It is well known that the key to maximize the sensitivity of an IFE-based fluorescence assays is to broaden the overlap between the absorption of an absorber and the excitation/emission of a fluorophore. We employed CuInS/ZnS quantum dots (CIS/ZnS QDs) and p -nitrophenylphosphate (PNPP) as the fluorescent indicator and the substrate, respectively, for ALP activity assessment. Due to the CIS/ZnS QDs have an efficient excitation at 405 nm, meanwhile with a large Stokes shift emission at 588 nm, p -nitrophenol (PNP) with absorption peak at 405 nm, the hydrolyzed produce of PNPP and ALP, can act as a competitive absorber to absorb the excitation light of CIS/ZnS QDs, resulting in noticeable quenching of CIS/ZnS QDs. The proposed sensor detects ALP activity in human serum samples (sample consumption: 20 μL) with detection limit of 0.01 U L -1 . Excellent biocompatibility of CIS/ZnS QDs enables the sensor to monitor endogenous ALP in living cells. Furthermore, because the surface modification or the linking between the receptor and the fluorophore is no longer required, this fluorescent sensing system has the potential to simplify ALP clinical measurement, thereby improving diagnostics of relevant diseases. [ABSTRACT FROM AUTHOR]

Benefiting from the excellent photostability and biocompatibility, fluorescent nanoclusters have recently emerged as a highly attractive bio-sensing and imaging material, especially in early diagnosis of cancer. However, their clinic applications were limited by the unsatisfactory specificity and the complex synthesis. In this study, novel methionine coated gold nanoclusters (Met-AuNCs) have been prepared via an easily-achievable one-pot synthetic method. The prepared Met-AuNCs showed high imaging-specificity: after incubating with Met-AuNCs for 1 h, cancer cells (including A549, Hela, MCF-7, HepG2) were fluorescent, while the normal cells (WI-38 and CHO) showed no fluorescence. According to a series of controlled experiments, the reason for the high imaging-selectivity was proposed to originate from the specific recognition of L-type amino acid transporter overexpressed in cancer cells. [ABSTRACT FROM AUTHOR]

This work reports an approach for imaging the localization, distribution, and level of miRNA in different organelles based on an activated fluorescence signal triggered by an alteration of the specific binding-induced conformation of the designed activatable probe. We selected miR-150 as an miRNA example to image its localization, distribution, and level in human cervical cancer cells (HeLa cells). The results indicate that miR-150 is localized and distributed in different subcellular organelles (mainly in mitochondria and lysosomes) and that its levels (actually its concentrations) in lysosomes are higher than those in mitochondria in both HeLa and MCF-7 cells. Moreover, the level of miRNA in cells is displayed in a height-dependent (in z-direction) manner. This approach can also be used to image the localization and distribution of various miRNAs (such as miR-150 and miR-214) in different organelles in cancer cells simultaneously. The probes exhibit high resistance to cellular endo- and exonucleases, with high specificity; the capability of avoiding false signals, with a high signal-to-background ratio; and a good ability to operate in complicated environments. The developed approach may provide a useful tool for studying the localization and distribution and evaluating the level of multiple tumor-related miRNAs in cells. [ABSTRACT FROM AUTHOR]

Particles which bear tumor cell targeting and multimode imaging capabilities are promising in tumor diagnosis and cancer therapy. A simple and versatile method to fabricate gold/polydopamine-Methylene Blue@Bovine Serum Albumin–glutaraldehyde–Transferrin composite particles (Au/PDA-MB@BSA-GA-Tf NPs) for tumor cell targeting and fluorescence (FL) / surface-enhanced Raman scattering (SERS) dual-modal imaging were reported in this work. Polydopamine (PDA) spheres played an important role in gold ion reduction, gold nanoparticle (Au NPs) binding and methylene blue (MB) adsorption, MB were employed as both fluorescence label and Raman reporter. In addition, glutaraldehyde (GA) crosslinked bovine serum albumin (BSA) in the outer layer of Au/PDA-MB nanoparticles can prevent MB from dissociation and leakage. The composite nanoparticles were further conjugated with transferrin (Tf) to target transferrin receptor (TfR)-overexpressed cancer cells. The targeting ability as well as the intracellular location of the probe was investigated through SERS mapping and fluorescence imaging. Their excellent biocompatibility was demonstrated by low cytotoxicity against breast cancer cell (4T1 cell). [ABSTRACT FROM AUTHOR]

Nowadays, cancer has become a serious threat to public health worldwide. Early and precise diagnosis is critical for the detection, monitoring and management of cancer. Herein, a facile strategy for developing a fluorescence/MRI dual-modal nanoprobe (FA-PEI-NaGdF 4 :Eu nanoparticles) has been reported for targeted cancer cell imaging. The fluorescence/MRI nanoprobes have strong fluorescence and the high signal-to-noise ratio, which is suitable for the fluorescence imaging. Moreover, the FA-PEI-NaGdF 4 :Eu nanoprobes have high longitudinal relaxivity, making them suitable for T 1 -weighted MR imaging. Additionally, due to modification with FA, the fluorescence/MRI nanoprobes could target cancer cells that possessed large numbers of folate receptors. The results of the cytotoxicity assay revealed that the nanoprobes had the excellent biocompatibility. With the high biocompatibility, excellent imaging performance and superior targeting, the FA-PEI-NaGdF 4 :Eu nanoprobes can be used as a promising candidate for targeted fluorescence/MRI cancer cell imaging and would bring more opportunities for the biomedical applications. [ABSTRACT FROM AUTHOR]

A bioorthogonal Raman reporter-embedded Au-core and polydopamine-shell nanoprobe was initially designed and synthesized for live cell surface-enhanced Raman scattering (SERS) imaging in Raman-silent region. The firstly synthetic bioorthogonal Raman reporter (E)-2- ((4-(phenylethynyl) benzylidene)amino)ethanethiol (PBAT) provided intense Raman signal at 2220cm-1 in Raman-silent region. And its synthetic method was environmentally benign, high yield and easy in operation. In addition, the hydrophobicity of PBAT led to slightly aggregation of gold nanoparticles, which enhance the SERS intensity of the nanoprobe through hot spots. Furthermore, owing to the remarkable biocompatibility of polydopamine (PDA), the SERS nanoprobe can be smoothly internalized into cancer cells to realize SERS imaging in Raman-silent region. Finally, the SERS mapping results confirmed that nanoprobe exhibited strong SERS signal intensity, excellent stability in complex biological environment and low toxicity inside live cancer cells. Therefore, the reporter-embedded core-shell nanoprobe has enormous potential of applications in biomedical diagnostics in the near future. Graphical abstractHighlights· One-step synthetic method of thiol and alkynyl contained bioorthogonal SERS reporter is environmentally benign, high yield and easy in operation. · Au@PBAT@PDA nanoparticles exhibit strong SERS signal intensity, excellent stability in complex biological environment. · Au@PBAT@PDA nanoparticles show good imaging results for live cancer cell SERS imaging in Raman-silent region. · The rich functional groups (i.e., catechol and amine) on PDA surface provide a broad platform for further modification in biomedical application. · A Raman-silent region nanoprobe was synthesized for live cell SERS imaging. [ABSTRACT FROM AUTHOR]

5 nm intense green emission NaYF 4 :Yb/Er upconversion nanoparticles (UCNPs) with pure β phase was synthesized with a simple “green” strategy for the first time. Traditional organic solvothermal method is often applied to prepare the high-quality and uniform UCNPs, but the preparation of lanthanide-oleate complexes is laborious as heating and multistep post-treatment for purification are often required. The water-alcohols solvothermal method is environmentally friendly, but the fabricated UCNPs have big size, poor biocompatibility and high cytotoxicity, which limited their application for cell imaging. Herein, NaYF 4 :Yb/Er UCNPs were prepared with rare-earth nitrates RE(NO 3 ) 3 (RE=Y 0.80 Yb 0.18 Er 0.02 ) as precursors and diethylene glycol (DEG)/ethylene glycol (EG)/water as the solvent. A facile green solvothermal method with the temperature being controlled at 300 °C was developed. The as-prepared NaYF 4 :Yb/Er UCNPs were characterized and were found to have enhanced UC emission and controllable particle size. The as-prepared UCNPs were further functionalized via folic acid coating for the targeted imaging and improved bio- compatibility. It was made the UCNPs potential for upconversion bioimaging of living cells by the strong upconversion luminescence, the excellent biocompatibility, and the super-small size. The good colloidal stability and low cell cytotoxicity of the as-prepared UCNPs and the developed synthesis protocol might advance both the fields of UCNPs and biomolecule-based nanotechnology for future studies. [ABSTRACT FROM AUTHOR]

A label-free electrochemiluminescence (ECL) cytosensor was developed for dynamically evaluating of epidermal growth factor receptor (EGFR) expression on MCF-7 cancer cells based on the specific recognition of epidermal growth factor (EGF) with its receptor (EGFR). EGF-cytosensor was fabricated by in-situ electro-polymerization of polyaniline as substrate, using CdS quantum dots (CdS QDs) as ECL probe and gold nanoparticles (AuNPs) as a carrier for loading of EGF. AuNPs and CdS QDs were jointly attached on polyaniline surface to provide a sensitive and stable sensing interface, as well as a simple and label-free mode for ECL assay. Electron microscopy, atomic force microscopy (AFM) and electrochemical methods were employed to characterize the multilayer construction process of the sensing interface. The proposed EGF-cytosensor exhibited excellent analytical performance for MCF-7 cancer cells, ranging from 12 to 1.2×10 6 cells mL −1 , with a low detection limit of 12 cells mL −1 . Also, it was successfully applied in evaluating EGFR expression of cells surface, which was stimulated by some inhibitors or activator, and the results were confirmed by using flow cytometry and laser scanning confocal microscopy analysis. The proposed ECL cytosensor has potential applications in monitoring the dynamic variation of receptor molecules expression on cell surfaces in response to external stimulation by drugs and screening anti-cancer therapeutic agents. [ABSTRACT FROM AUTHOR]

Surface-Enhanced Raman scattering (SERS) has been widely used for imaging and sensing. However, limited reports are currently available on SERS-based cancer cell targeting strategy due to the challenge of synthesizing highly sensitive, reproducible and biocompatible SERS probe. Herein, we developed novel SERS probes, based on BSA (Bull Serum Albumin) coated gold–silver core–shell nanorods modified with Raman reporter 5,5-dithiobis 2-nitrobenzoic acid (DTNB) (Au@AgNRs@BSA@Anti-MICA), for in vitro cancer cell detection. Our results demonstrate that the SERS probe is very robust for cancer cell ultrasensitive detection with good biocompatibility and strong SERS signal. [ABSTRACT FROM AUTHOR]

In this study, double shelled NIR CdSeTe/CdS/C quantum dots (QDs) were synthesized by a liquid phase method. The as-prepared QDs showed low cytotoxicity and good biocompatibility due to the formation of carbon shell. The imaging of targeted Human cervical carcinoma cells (HeLa cells) indicates that the CdSeTe/CdS/C QDs have excellent optical properties and cell viability. These results clearly shows that the CdSeTe/CdS/C QDs can be a good candidate for bioapplications. [ABSTRACT FROM AUTHOR]

Mucin 1 (MUC1) overexpression in tumor cells is related to various cancers, including breast, stomach, and lung cancer. MUC1 detection and imaging are important for cancer localization in tissue sections to support histopathological diagnosis. In this study, we developed a simple, enzyme-free MUC1 detection and in situ imaging method. Three hairpin probes, Apt-trigger, HP1-FAM, and HP2, were designed for MUC1 recognition and hybridization chain reaction (HCR). The Apt-trigger probe was composed of two sequences: the MUC1 aptamer and HCR trigger sequence. The 5' end of the HP1-FAM probe was modified with a FAM signal molecule. In the presence of MUC1, the aptamer sequence is activated and bound to MUC1, which opens the hairpin structure. Then, the trigger sequence gets exposed and, complementary to HP1-FAM, triggers a continuous HCR process. This method was successfully used to detect MUC1 of 200 pM–25 nM and MUC1 in situ imaging in specific cells, such as human breast carcinoma (MCF-7) and human colon cancer (HT-29) cells. A simple, enzyme-free detection and in situ imaging method for MUC1 was developed. This method was not only successfully used for MUC1 detection, but also its in situ imaging in specific cells. [Display omitted] • A simple, enzyme-free detection and in situ imaging method for MUC1 was developed. • An aptamer conformational switch was used for MUC1 recognition. • The hybridization chain reaction (HCR) was used for signal amplification. • This approach has potential applications in the detection and in situ imaging of various proteins. [ABSTRACT FROM AUTHOR]

Abstract: Herein, one multifunctional AS1411-functionalized fluorescent gold nanoparticles (named NAANPs) is synthesized and successfully applied for both targeted cancer cell imaging and efficient photodynamic therapy (PDT). The NAANPs are obtained by functionalizing the gold nanoparticles with AS1411 aptamer and then bound with one porphyrin derivative N-methylmesoporphyrin IX (NMM). Using HeLa cells over expressing nucleolin as representative cancer cells, the formed NAANPs can target to the cell surface via the specific AS1411-nucleolin interaction, which can discriminate the cancer cells from normal ones (e.g. HEK293) unambiguously. That the fluorescence intensity of NMM increased significantly upon binding to AS1411 G-quadruplex makes the NAANPs appropriate fluorescence reagent for cell imaging. Meanwhile, NMM can also be used as a photosensitizer, thus irradiation of the NAANPs by the white light from a common electric torch can lead to efficient production of cytotoxic reactive oxygen species for establishing a new type of PDT to cancer cells. Gold nanoparticles play the roles of both carrier and enhancer of the functional groups onto the cells. In addition, they not only possess inherently certain cytotoxicity to the cancer cells, but also boost the cellular uptake of the fluorescent groups. As a result, the efficiency of both the targeted cell imaging and PDT could be ensured. [Copyright &y& Elsevier]

Abstract: Multifunctional fluorescent silica nanoparticles with phenylboronic acid tags were developed for labeling sialic acid on the surface of living cancer cells. In this paper, fluorescent silica nanoparticles (FSNPs) with strong and stable emission at 515nm were firstly prepared through a reverse microemulsion process, and then modified with highly selective phenylboronic acid (PBA) tags on their surface via an aqueous ‘thiol-ene’ click reaction. These nanoparticles had a hydrodynamic diameter of 92.6±9.1nm, and a bright fluorescence signal, which is 366 times higher than that of a single dye molecule. Meanwhile, these PBA-tagged FSNPs were found very stable in aqueous solution as well as in cell culture medium, verified by transmission electron microscopy, X-ray photoelectron spectroscopy and zeta potential analysis. The over-expressed sialic acid (SA) on the membrane of living HeLa cells was visualized in situ by a confocal laser scanning microscopy, ascribed to the specific interaction between PBA and SA. Thus, the PBA-FSBPs showed a great potential in probing SA expressed on living cells with high selectivity and sensitivity. [Copyright &y& Elsevier]

Development of noninvasive bioimaging fluorescent probes for detecting particular enzyme activity is greatly recommendable for preclinical diagnosis of cancer. Given that the elevated β-gal activity is positively correlated with several tumors, developing a fluorescent probe for the sensing of β-gal is therefore highly desirable for cancer diagnosis. Herein, a new enzyme-activatable near-infrared (NIR) turn-on fluorescent probe (DMC-βgal) was developed for accurately detecting β-gal activity characterized by excellent selectivity, high sensitivity (LOD = 0.298 U/L), and low toxicity. More importantly, DMC-βgal qualifies remarkable NIR excitation (725 nm) and emission wavelength (770 nm), an ideal tool for restrained photodamage and suppressed autofluorescence. The above excellent performance of DMC-β-gal allowed for the accurate monitoring of endogenous β-gal in living cells. Moreover, the probe was successfully applied to detect intracellular β-gal activity in different types of cancer cells, verifying that SKOV-3 cells had a higher level of β-gal activity than those of A549, HCT-116, MCF-7, and HepG2 cells. Furthermore, DMC-βgal could real-time visualize endogenously β-gal in tumor-bearing nude mice with low auto-fluorescence interference. All results fully demonstrated that DMC-βgal has potential value as a promising strategy for diagnosis of β-gal-related diseases. [Display omitted] • A new near-infrared excited and emitted β-galactosidase (β-gal) fluorescent probe DMC-βgal was synthesized. • The probe DMC-βgal is characterized by excellent selectivity and high sensitivity (LOD = 0.298 U/L). • The probe is applied to prove that the β-gal activity in SKOV-3 cells is higher than HepG2, A549, HCT-116, MCF-7 cells. • DMC-βgal can real-time visualize the β-gal activity in tumor-bearing nude mice with low photodamage and autofluorescence. [ABSTRACT FROM AUTHOR]

Ascorbic acid (AA) and glutathione (GSH), the most abundant intracellular reductive substances, have been widely used as biomarkers for cancer cells identification. The current methods relying on imaging of AA or GSH alone to identify cancer cells may cause systematic errors, since a mutual conversion relationship exists between AA and GSH. In this work, we propose a fluorescent nanosensor for the simultaneous imaging of intracellular reductive substances including AA and GSH. Biocompatible fluorescent silicon nanoparticles (SiNPs) with rich surface amine and carboxyl groups were synthesized. The fluorescence of the SiNP was initially quenched by chelation of Fe3+ ions, forming SiNP/Fe3+ complex as the fluorescent nanosensor. Upon the redox reaction with reductive substances, the nanosensor showed sensitively fluorescent recovery. Moreover, benefited from the efficient cellular uptake of the SiNP/Fe3+ and the overexpressed intracellular reductive substances in cancer cells, the fluorescent nanosensor was used to accurately identify the human breast carcinoma (MCF-7) cells from normal mammary epithelial (MCF-10A) cells by imaging of intracellular AA and GSH simultaneously. This strategy would be promising in imaging-guided precision cancer diagnosis. [Display omitted] • A SiNPs-based response to reductive substances fluorescent nanosensor was developed. • The good sensitivity and selectivity were obtained. • The nanosensor was utilized to image reductive substances in cell with satisfactory results. • Cancer cell identification was completed by the facile fluorescent nanosensor. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, different sizes of glutathione-capped CdTe (GSH/CdTe) quantum dots (QDs) have been prepared directly in aqueous solution. The QDs have tunable fluorescence in the range of 510–670nm, and they also have high photoluminescence quantum yield (PLQY) without any postpreparative treatment. Furthermore, the QDs have strong resistance to photobleaching, and they also have to be considered as cytocompatible. In addition, for the first time, folic acid was covalently conjugated to the GSH/CdTe QDs for imaging of cancer cells, demonstrating their potentially broad application as biolabels. [ABSTRACT FROM AUTHOR]

Photoluminescent gold nanoclusters have attracted an extensive research interest in bioimaging and therapeutics due to several distinctive advantages such as high fluorescent photostability, good dispersibility, low toxicity and large Stokes shift. However, a better understanding of the correlation between optical properties in various environments and their uptake by specific cancer cells is still needed. Herein, we developed bovine serum albumin stabilized gold nanoclusters (BSA-AuNCs) with an intrinsic tunable photoluminescence emission in the first biological window. The as-synthetized BSA-AuNCs agents consists in protein polymerized-chains dopped with AuNCs with an average size of 2–3 nm and were found to exhibit relevant properties as high photostability, temperature-dependent and excitation induced tunable red photoluminescence. The photostable BSA-AuNCs were functionalized with folic acid (FA-BSA-AuNCs) in order to achieve for the first time an active targeting of NIH:OVCAR-3 human ovarian adenocarcinoma cells, via AuNCs, towards bioimaging applications. After confirming their biocompatibility up to a concentration of 40 mg/ml, the improved cellular uptake and staining ability of FA-BSA-AuNCs compared to the BSA-AuNCs was validated by conventional wide-field epi-fluorescence microscopy, while the intracellular localization was monitored by confocal fluorescence lifetime imaging microscopy (FLIM). Considering their valuable intrinsic photoluminescent properties, the synthesized FA-BSA-AuNCs hold great promise for direct application in cellular imaging as efficient contrast agents towards early cancer diagnosis and image-guided therapy of cancer. Image 1 • Biocompatible gold nanoclusters stabilized with bovine serum albumin protein. • Reversible temperature-dependent and excitation induced tunable photoluminescence. • Active targeting of ovarian cancer cells via functionalization with folic acid. • Efficient performance as cancer-specific fluorescent contrast agents via FLIM. [ABSTRACT FROM AUTHOR]

Superoxide anion (O 2 •-) is an important biomarker for reactive oxygen species (ROS) generated through physiological and pathological processes. However, due to the short half-life of O 2 •- and high autofluorescence of cell tissues, in situ real-time tracking and monitoring of endogenous O 2 •- can be difficult. In this paper, a fluorescent probe IFP-O 2 was developed to detect endogenous O 2 •- in cells. The probe could instantaneously react with O 2 •- to produce fluorescence off-on effect; its detection limit was as low as 10 nM. Cell experiments also showed that the probe had low toxicity and mitochondrial targeting ability. The article presents, for the first time, a probe that can be employed to measure endogenous O 2 •- in oral cancer Cal-27 cells and is a promising tool for monitoring and evaluating apoptosis. Image 1 [ABSTRACT FROM AUTHOR]

Bimodal photoluminescence-magnetic resonance (MR) imaging technique has attracted tremendous attention due to its great potential in biomedical researches and clinical practices. Herein a novel multifunctional magnetoluminescent nanocomposite, FA-Gd-Tb@SiO 2 , was found to serve as an effective probe for bimodal time-gated luminescence/MR imaging of cancer cells in vitro and in vivo. The nanoprobe was designed by integrating a luminescent Tb3+ complex, a Gd(III)-based contrast agent and a tumor-targeting molecule, folic acid (FA), into a silica nanoparticle. The integration of these functional moieties allows the nanoprobe to be employed for specific imaging of cancer cells with background-free TGL and non-invasive MR imaging modes. In addition, the optical and magnetic properties were dramatically improved after implicating the newly synthesized nanoarchitecture. In vitro cellular TGL imaging demonstrated that the FA-Gd-Tb@SiO 2 nanoprobe could recognize and accumulate in cancer cells overexpressing FA receptor. Furthermore, in vivo study revealed that the as-prepared nanoprobe was able to effectively enhance T 1 -weighted MR contrast and TGL intensity in tumor tissue, which might contribute to the precise detection and tracing of cancer cells, as well as diagnosis and therapy of tumor in clinical. Multifunctional magnetoluminescent silica nanoparticles for tumor-targeted time-gated luminescence/magnetic resonance imaging in vitro and in vivo. Image 1 • Multifunctional tumor-targetable silica nanoparticles for bimodal TGL/MR imaging of cancer cells were developed. • The nanoprobe can be employed for imaging of cancer cells with both background-free TGL and non-invasive MR imaging modes. • The nanoprobe can visualize tumors with various resolutions (from single cell to whole living body) and no depth limit. • The bimodal TGL/MR imaging method can improve the accuracy of cancer diagnosis and minimize potential artifacts. [ABSTRACT FROM AUTHOR]

Protein-encapsulated gold nanoclusters (Au NCs) have recently gained much attention in biosensing and bioimaging applications owing to their remarkable fluorescence properties, nontoxicity and good biocompatibility. In this work, the mannose was grafted onto the bovine serum albumin (BSA) encapsulated Au NCs (BSA-Au NCs) to produce a mannose functionalized BSA-Au NCs (Man-BSA-Au NCs) as a new fluorescence probe for Concanavalin A (Con A) detection and human breast cancer cell imaging. A new strategy with mannose-BSA conjugates as template was firstly applied for the synthesis of Man-BSA-Au NCs, leading to a high loading of mannose (767.6 ± 7.2 mg/L) onto BSA-Au NCs. The as-prepared Man-BSA-Au NCs showed advantages of facile preparation, good monodispersity and strong red-emission. Notably, aggregation-induced fluorescence quenching of Man-BSA-Au NCs was triggered by Con A due to the multivalent cooperative interactions between mannose and Con A, which was subsequently confirmed by MALDI-TOF MS. Hence highly selective and sensitive fluorescence detection of Con A was achieved by using Man-BSA-Au NCs as a fluorescence sensor. A good linear relationship was obtained over the range of 0.01–1 μM (R2 = 0.994) with a detection limit of 0.62 nM (S/N = 3). The developed sensor was then applied to determine Con A in human serum with acceptable recoveries of 93.70–104.8%. Moreover, based on the specific recognition between mannose and overexpressed mannose receptors on human breast cancer cells, the Man-BSA-Au NCs were successfully utilized for cancer cell imaging with good specificity. Image 1 • Man-BSA-Au NCs with high mannose loading were facilely prepared with new strategy. • Con A triggered an aggregation-induced "fluorescence quenching" of Man-BSA-Au NCs. • Man-BSA-Au NCs showed good sensitivity and selectivity for Con A sensing. • Man-BSA-Au NCs showed good specificity for human breast cancer cell imaging. [ABSTRACT FROM AUTHOR]

Targeted imaging of cancer cells is crucial for early diagnosis. Mucin is a transmembrane protein that is overexpressed by cancer cells and is considered a cancer target. Specific recognition of mucin by aptamers has been receiving increasing attention in recent years. In this study, we use DNA MUC1 aptamer as a protective agent and target molecule in the synthesis of ultra-small fluorescent gold nanoclusters (MUC1-AuNCs) via a simple one-step method. MUC1-AuNCs exhibited red fluorescence emission with excellent stability over a wide pH range and under strong illumination. Confocal images showed that the synthesized MUC1-AuNCs efficiently targeted mucin overexpressing 4T1 cancer cells, but were not observed in 293T normal cells. Furthermore, the MUC1-AuNCs had a 5667 ns lifetime and 235 nm Stokes shifts and markedly eliminated background interference, suggesting they are a promising fluorescent probe for cell-targeted labeling and imaging. Image 1 • Luminescent gold nanoclusters were synthesized by thiolated MUC1 DNA aptamer as template. • The MUC1-AuNCs demonstrate good stability, low toxicity and specific cancer cell targeting properties. • The MUC1-AuNCs with long fluorescence lifetimes and large stokes shift can reduce background interference. [ABSTRACT FROM AUTHOR]

Monitoring hypochlorite anion (ClO−) in living cells is particularly meaningful and valuable, because over-exposure of the ClO− may cause a potential health hazard towards animals and humans. Considering the special structure and properties of the gemini surfactant, a novel amphiphilic gemini-iridium complex Ir[(ppy-iso) 2 (bpy-tma 2 Br 2)] (Ir-iso) with isoniazide as a recognition site for ClO− was designed. The Ir-iso possessed an excellent water-solubility as well as a strong ClO− binding capacity, as revealed from the rapid response of emission signal towards ClO−. It was worth noting that such probe had a highly-specific selectivity with a low detection limit (20.5 nM) and was suitable in physiological environment. The cell viability assay, cell imaging, and co -location studies further proved that the Ir-iso had little cytotoxicity and was specifically localized in the mitochondria of breast cancer cells, being a promising candidate of chemo-sensor to detect the endogenous ClO− in living cells. Image 1 • A novel Ir-iso sensor with isoniazide as a recognition site for the detection of ClO− is presented. • The sensor exhibits a significantly improved water-solubility and a strong ClO− binding capacity. • The sensor is capable of detecting 20.5 nM of ClO− in physiological environment with a highly specific selectivity. • Little cytotoxicity and mitochondria-targeted phosphorescence probe for the detection of endogenous ClO−. [ABSTRACT FROM AUTHOR]