Oluwasesan Adegoke

Challenges and advances in quantum dot fluorescent probes to detect reactive oxygen and nitrogen species: a review.

The pathological and physiological effects of reactive oxygen and nitrogen species (ROS/RNS) have instigated increasing awareness in the scientific field with respect to the development of suitable probes for their detection. Among the various probes developed to date, semiconductor quantum dots (QDs) fluorescent probes have attracted significant attention. The unfavourable properties of ROS/RNS with respect to their detection, such as their short lifetimes and the competitive presence of various endogenous reactive species, capable of interfering with the probe in biological matrices, have hindered the effective performance of most probes as well as complicating the design of suitable probes. The development of novel QD fluorescent probes capable of circumventing these problems is thus, of scientific interest. In this review, we highlight the challenges faced, pros and cons and published developments to date, with respect to QD fluorescent probes for ROS/RNS such as H2O2, O2(·-), ·OH, HOCl, NO and ONOO(-).

Synthesis and characterization of quantum dots designed for biomedical use

Semiconductor quantum dots (QDs) have become promising nanoparticles for a wide variety of biomedical applications. However, the major drawback of QDs is their potential toxicity. Here, we determined possible cytotoxic effects of a set of QDs by systematic photophysical evaluation in vitro as well as in vivo. QDs were synthesized by the hydrothermal aqueous route with sizes in the range of 2.0-3.5 nm. Cytotoxic effects of QDs were studied in the human pancreatic carcinoid cell line BON. Cadmium telluride QDs with or without zinc sulfide shell and coated with 3-mercaptopropionic acid (MPA) were highly cytotoxic even at nanomolar concentrations. Capping with l-glutathione (GSH) or thioglycolic acid (TGA) reduced the cytotoxicity of cadmium telluride QDs and cadmium selenide QDs. Determination of the toxicity of QDs revealed IC50 values in the micromolar range. In vivo studies showed good tolerability of CdSe QDs with ZnS shell and GSH capping. We could demonstrate that QDs with ZnS shell and GSH capping exhibit low toxicity and good tolerability in cell models and living organisms. These QDs appear to be promising candidates for biomedical applications such as drug delivery for enhanced chemotherapy or targeted delivery of light sensitive substances for photodynamic therapy.

Versatility of a localized surface plasmon resonance-based gold nanoparticle-alloyed quantum dot nanobiosensor for immunofluorescence detection of viruses

Flu infection, caused by the influenza virus, constitutes a serious threat to human lives worldwide. A rapid, sensitive and specific diagnosis is urgently needed for point-of-care treatment and to control the rapid spread of this disease. In this study, an ultrasensitive, rapid and specific localized surface plasmon resonance (LSPR)-induced immunofluorescence nanobiosensor has been developed for the influenza virus based on a gold nanoparticle (AuNP)-induced quantum dot (QD) fluorescence signal. Alloyed quaternary CdSeTeS QDs were synthesized via the hot-injection organometallic route and were subsequently capped with l-cysteine via a ligand exchange reaction. AuNPs were synthesized in HEPES buffer and thiolated with l-cysteine. The concept of the biosensor involves the conjugation of anti-neuraminidase (NA) antibody (anti-NA Ab) to thiolated AuNPs and the conjugation of anti-hemagglutinin (HA) antibody (anti-HA Ab) to alloyed quaternary l-cysteine-capped CdSeTeS QDs. Interaction of the antigens displaying on the surface of the influenza virus target with anti-NA Ab-conjugated AuNPs and anti-HA Ab-conjugated QDs induces an LSPR signal from adjacent AuNPs to trigger fluorescence-enhancement changes in the QDs in proportion to the concentration of the target virus. The detection limit for influenza H1N1 virus was 0.03pg/mL in deionized water and 0.4pg/mL in human serum; while, for the clinically isolated H3N2, the detection limit was 10PFU/mL. The detection of influenza virus H1N1 was accomplished with high sensitivity. The versatility of the biosensor was demonstrated for the detection of clinically isolated influenza virus H3N2 and norovirus-like particles (NoV-LPs).

Gradient band gap engineered alloyed quaternary/ternary CdZnSeS/ZnSeS quantum dots: an ultrasensitive fluorescence reporter in a conjugated molecular beacon system for the biosensing of influenza virus RNA

Controlling and engineering the particle composition of semiconductor alloys is one of the topmost targets in the field of semiconductor materials science and technology. Quantum dot (QD) nanocrystals offer an unmatched opportunity to obtain a wide range of composition-controlled alloys and have captivated a great deal of interest recently. Herein, we report on band gap engineering via tuning and controlling the sulphur molar fraction (ternary shell layer) of quaternary/ternary core/shell alloyed CdZnSeS/ZnSeS QDs. Varying optical properties were exhibited by the alloyed QDs but a uniform particle size distribution was maintained across all the compositions. The alloyed QDs displayed bright emission colours under UV irradiation, whereas the photoluminescence quantum yields (PL QY) were in a remarkable range of 36-98%. Non-linearity of the lattice parameter was an indication of gradient alloying of the nanocrystals, whereas the kinetics of the optical properties unravelled the effect of intrinsic optical bowing. Displacement of bond length and anion mismatch influenced the optical properties of the QDs with respect to the variation in the PL QY. Alloyed CdZnSeS/ZnSe1.0S1.3 QDs with a spectacular PL QY were exploited as an ultrasensitive fluorescence reporter in a conjugated molecular beacon (MB) assay to detect influenza virus H1N1 RNA. Our detection system was rapid and highly sensitive for detecting extremely low concentrations of H1N1 RNA (down to 2 copies per mL), specific and versatile (detects H1N1 RNA in human serum). For proof of concept, the alloyed CdZnSeS/ZnSe1.0S1.3 QD-MB bioprobe exhibited a superior 12-fold sensitivity over an alloyed CdZnSeS-MB probe, while a conventional CdSe/ZnS-MB probe could not detect extremely low concentrations of influenza virus H1N1 RNA.

Size-confined fixed-composition and composition-dependent engineered band gap alloying induces different internal structures in L-cysteine-capped alloyed quaternary CdZnTeS quantum dots.

The development of alloyed quantum dot (QD) nanocrystals with attractive optical properties for a wide array of chemical and biological applications is a growing research field. In this work, size-tunable engineered band gap composition-dependent alloying and fixed-composition alloying were employed to fabricate new L-cysteine-capped alloyed quaternary CdZnTeS QDs exhibiting different internal structures. Lattice parameters simulated based on powder X-ray diffraction (PXRD) revealed the internal structure of the composition-dependent alloyed CdxZnyTeS QDs to have a gradient nature, whereas the fixed-composition alloyed QDs exhibited a homogenous internal structure. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis confirmed the size-confined nature and monodispersity of the alloyed nanocrystals. The zeta potential values were within the accepted range of colloidal stability. Circular dichroism (CD) analysis showed that the surface-capped L-cysteine ligand induced electronic and conformational chiroptical changes in the alloyed nanocrystals. The photoluminescence (PL) quantum yield (QY) values of the gradient alloyed QDs were 27–61%, whereas for the homogenous alloyed QDs, the PL QY values were spectacularly high (72–93%). Our work demonstrates that engineered fixed alloying produces homogenous QD nanocrystals with higher PL QY than composition-dependent alloying.

l-Cysteine-capped core/shell/shell quantum dot–graphene oxide nanocomposite fluorescence probe for polycyclic aromatic hydrocarbon detection

Environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), become widely distributed in the environment after emission from a range of sources, and they have potential biological effects, including toxicity and carcinogenity. In this work, we have demonstrated the analytical potential of a covalently linked L-cysteine-capped CdSeTe/ZnSe/ZnS core/shell/shell quantum dot (QD)-graphene oxide (GO) nanocomposite fluorescence probe to detect PAH compounds in aqueous solution. Water-soluble L-cysteine-capped CdSeTe/ZnSe/ZnS QDs were synthesized for the first time and were covalently bonded to GO. The fluorescence of the QD-GO nanocomposite was enhanced relative to the unconjugated QDs. Various techniques including TEM, SEM, HRSEM, XRD, Raman, FT-IR, UV/vis and fluorescence spectrophotometry were employed to characterize both the QDs and the QD-GO nanocomposite. Four commonly found priority PAH analytes namely; phenanthrene (Phe), anthracene (Ant), pyrene (Py) and naphthalene (Naph), were tested and it was found that each of the PAH analytes enhanced the fluorescence of the QD-GO probe. Phe was selected for further studies as the PL enhancement was significantly greater for this PAH. A limit of detection (LOD) of 0.19 µg/L was obtained for Phe under optimum conditions, whilst the LOD of Ant, Py and Naph were estimated to be ~0.26 µg/L. The fluorescence detection mechanism is proposed.

An ultrasensitive SiO2-encapsulated alloyed CdZnSeS quantum dot-molecular beacon nanobiosensor for norovirus.

Ultrasensitive, rapid and selective diagnostic probes are urgently needed to overcome the limitations of traditional probes for norovirus (NV). Here, we report the detection of NV genogroup II via nucleic acid hybridization technology using a quantum dot (QD)-conjugated molecular beacon (MB) probe. To boost the sensitivity of the MB assay system, an ultrasensitive QD fluorophore with unique optical properties was synthesized, characterized and exploited as a fluorescence signal generator. Alloyed thioglycolic (TGA)-capped CdZnSeS QDs with a high photoluminescence (PL) quantum yield (QY) value of 92% were synthesized, and a modified silanization method was employed to encapsulate the thiol-capped QDs in a silica layer. The resulting highly luminescent alloyed SiO2-coated CdZnSeS QDs had a remarkable PL QY value of 98%. Transmission electron microscopy and dynamic light scattering confirmed the monodispersity of the alloyed nanocrystals, and zeta potential analysis confirmed their colloidal stability. Powder X-ray diffraction and PL lifetime measurements confirmed the surface modification of the QDs. The alloyed TGA-capped and SiO2-coated CdZnSeS QD-conjugated MB bioprobes detected extremely low concentrations of NV RNA. Ultrasensitive detection of low concentrations of NV RNA with a limit of detection (LOD) of 8.2copies/mL in human serum and a LOD of 9.3 copies/mL in buffer was achieved using the SiO2-coated CdZnSeS QD-MB probes, an increase in sensitivity of 3-fold compared with the detection limit for NV RNA using TGA-capped CdZnSeS QD-MBs. The additional merits of our detection system are rapidity, specificity and improved sensitivity over conventional molecular test probes.

An ultrasensitive alloyed near-infrared quinternary quantum dot-molecular beacon nanodiagnostic bioprobe for influenza virus RNA.

Conventional techniques used to diagnose influenza virus face several challenges, such as low sensitivity, slow detection, false positive results and misinterpreted data. Hence, diagnostic probes that can offer robust detection qualities, such as high sensitivity, rapid detection, elimination of false positive data, and specificity for influenza virus, are urgently needed. The near-infrared (NIR) range is an attractive spectral window due to low photon absorption by biological tissues, hence well-constructed fluorescent biosensors that emit within the NIR window can offer an improved limit of detection (LOD). Here, we demonstrate the use of a newly synthesized NIR quinternary alloyed CdZnSeTeS quantum dots (QDs) as an ultrasensitive fluorescence reporter in a conjugated molecular beacon (MB) assay to detect extremely low concentrations of influenza virus H1N1 RNA. Under optimum conditions, two different strains of influenza virus H1N1 RNA were detected based on fluorescence enhancement signal transduction. We successfully discriminated between two different strains of influenza virus H1N1 RNA based on the number of complementary nucleotide base pairs of the MB to the target RNA sequence. The merits of our bioprobe system are rapid detection, high sensitivity (detects H1N1 viral RNA down to 2 copies/mL), specificity and versatility (detects H1N1 viral RNA in human serum). For comparison, a conventional CdSe/ZnS-MB probe could not detect the extremely low concentrations of H1N1 viral RNA detected by our NIR alloyed CdZnSeTeS-MB probe. Our bioprobe detection system produced a LOD as low as ~1 copy/mL and is more sensitive than conventional molecular tests and rapid influenza detection tests (RIDTS) probes.

Unsymmetrically Substituted Nickel Triazatetra-Benzcorrole and Phthalocynanine Complexes: Conjugation to Quantum Dots and Applications as Fluorescent “Turn ON” Sensors

We report on the design and application of fluorescent nanoprobes based on the covalent linking of L-glutathione-capped CdSe@ZnS quantum dots (QDs) to newly synthesized unsymmetrically substituted nickel mercaptosuccinic acid triazatetra-benzcorrole (3) and phthalocyanine (4) complexes. Fluorescence quenching of the QDs occurred on conjugation to complexes 3 or 4. The nanoprobes were selectively screened in the presence of different cations and Hg2+ showed excellent affinity in “turning ON” the fluorescence of the nanoprobes. Experimental results showed that the sensitivity of QDs-4 towards Hg2+ was much higher than that of QDs-3 nanoprobe. The mechanism of reaction has been elucidated based on the ability of Hg2+ to coordinate with the sulphur atom of the Ni complex ring and apparently “turn ON” the fluorescence of the linked QDs.

CdTe quantum dots functionalized with 4-amino-2,2,6,6-tetramethylpiperidine-N-oxide as luminescent nanoprobe for the sensitive recognition of bromide ion

A novel bromide ion-selective modified nanoprobe sensor based on 4-amino-2,2,6,6-tetramethylpiperidine-N-oxide (4AT)-functionalized CdTe quantum dots (QDs-4AT) has been developed. Fluorescence quenching of the QDs by 4AT was observed. The functionalized QDs-4AT nanoprobe allowed a highly sensitive determination of bromide ion via analyte-induced change in the photoluminescence (fluorescence recovery) of the modified QDs. A detection limit of 0.6 nM of bromide ion was obtained, while the interfering effect of other inorganic cations and anions was investigated to examine the selectivity of the nanoprobe. The linear range was between 0.01 and 0.13 μM. Combined fluorescence lifetime and electron paramagnetic resonance measurements confirmed electron transfer processes between bromide ion and QDs-4AT.