There was much interest in the development of nanoscale delivery vehicles based on polymeric micelles to realize the diagnostic and therapeutic applications in biomedicine. Here, with the purpose of constructing a micellar magnetic resonance imaging (MRI) contrast agent (CA) with well biocompatibility and targeting specificity, two types of amphiphilic diblock polymers, mPEG–PG(DOTA(Gd))-b-PCL and FA-PEG-b-PCL, were synthesized to form mixed micelles by coassembly. The nanostructure of the resulting micellar system consisted of poly(caprolactone) (PCL) as core and poly(glycerol) (PG) and poly(ethylene glycol) (PEG) as shell, simultaneously modified with DOTA(Gd) chelates and folic acid (FA), which afforded functions of MRI contrast enhancement and tumor targeting. The mixed micelles in aqueous solution presented a hydrodynamic diameter of about 85 nm. Additionally, this mixed micelles exhibited higher r1 relaxivity (14.01 mM–1 S1–) compared with commercial Magnevist (3.95 mM–1 S1–) and showed negligible cytotoxicity estimated by WST assay. In vitro and in vivo MRI experiments revealed excellent targeting specificity to tumor cells and tissue. Furthermore, considerably enhanced signal intensity and prominent positive contrast effect were achieved at tumor region after tumor-bearing mice were intravenously injected with the mixed micelles. These preliminary results indicated the potential of the mixed micelle as T1 MRI CA for tumor-targeted imaging.

Recovering pure and viable circulating tumor cells (CTCs) from blood has been a challenging task for molecular characterization and functional analysis, which has attracted wide attention these days. Herein, we fabricate a thermoresponsive chitosan nanofiber substrate to effectively capture, purify, and release the target cancer cells, assisted by PNIPAAm brushes and DNA hybridization. The PNIPAAm brushes are designed to enable WBCs to detach from aptamer-PNIPAAm-chitosan-nanofiber (aptamer-P-CNFs) surfaces during the conformational transition. Meanwhile these specific captured CTCs are retained at a high purity. Moreover, effective and intact release of CTCs from the substrates without any foreign agents is realized by complementary sequences efficiently hybridizing with aptamers, and the specific cell release makes CTCs further purified. The present work provides a new strategy in the design of biointerface for recovering target CTCs from whole blood samples with high purity.Keywords: chitosan nanofiber; CTCs; nondestructive release; purification; thermoresponsive;

This is high demand to enhance the accumulation of near-infrared theranostic agents in the tumor region, which is favorable to the effective phototherapy. Compared with indocyanine green (a clinically applied dye), IR-780 iodide possesses higher and more stable fluorescence intensity and can be utilized as an imaging-guided PTT agent with laser irradiation. However, lipophilicity and short circulation time limit its applications in cancer imaging and therapy. Moreover, solid lipid nanoparticles (SLNs) conjugated with c(RGDyK) was designed as efficient carriers to improve the targeted delivery of IR-780 to the tumors. The multifunctional cRGD-IR-780 SLNs exhibited a desirable monodispersity, preferable stability and significant targeting to cell lines overexpressing αvβ3 integrin. Additionally, the in vitro assays such as cell viability and in vivo PTT treatment denoted that U87MG cells or U87MG transplantation tumors could be eradicated by applying cRGD-IR-780 SLNs under laser irradiation. Therefore, the resultant cRGD-IR-780 SLNs may serve as a promising NIR imaging-guided targeting PTT agent for cancer therapy.Keywords: c(RGDyK); imaging-guided therapy; IR-780 dye; near-infrared; photothermal therapy; solid lipid nanoparticles;

Gadolinium-based nanoscale magnetic resonance imaging (MRI) contrast agents (CAs) have gained significant momentum as a promising nanoplatform for detecting tumor tissue in medical diagnosis, due to their favorable capability of enhancing the longitudinal relaxivity (r1) of individual gadolinium ions, delivering to the region of interest a large number of gadolinium ions, and incorporating different functionalities. This mini-review highlights the latest developments and applications, and simultaneously gives some perspectives for their future development.

Herein, we fabricated efficient MR imaging probes by incorporating gadolinium oxide nanoparticles (Gd2O3) and gadolinium hybrid nanoparticles (GH) within RBCs. The Gd2O3 and GH encapsulated in the RBCs exhibited high relaxation rates and revealed high sensitivity for T1 MR imaging.

•Aptamers was obtained for dimethylindole red, an anionic derivative of cyanine dye.•A shortened 42-mer aptamer with sub-micromolar dissociation constant was selected.•The aptamer showed 140-fold fluorescence enhancement with interaction with DIR.To develop novel label-free light-up probes with improved performance characteristics and low background, we selected DNA aptamers for dimethylindole red (DIR) by a modified affinity chromatography based SELEX method. DIR is an anionic propylsulfonate substituted red-emitting dye derivative of thiazole orange and exhibited weak fluorescence in fluid solution and in the presence of dsDNA. After 14 rounds of selection, a shortened 42-mer DNA aptamer with sub-micromolar dissociation constant (Kd=0.65±0.17 μM) was selected. The fluorescent intensity of DIR was dramatically enhanced in the presence of the specific aptamer. The aptamer gave a 140-fold fluorescence enhancement in a saturated concentration. The DIR-aptamer pair could be potentially used as novel light-up fluorescent probe to construct sensors for various applications.Download high-res image (190KB)Download full-size image

Quinaldine red as a new fluorescent probe for i-motif structures was reported for the first time. When binding to i-motifs, quinaldine red exhibits a remarkable increase in its fluorescence, which benefits i-motif-involved label-free systems.

Quinaldine red as a new fluorescent probe for i-motif structures was reported for the first time. When binding to i-motifs, quinaldine red exhibits a remarkable increase in its fluorescence, which benefits i-motif-involved label-free systems.

In an attempt to explore a convenient and efficient strategy for constructing tumor-targeted T1 macromolecular contrast agents for magnetic resonance imaging, hyperbranched poly(glycerol) with good biocompatibility was used as a nanoplatform to conjugate gadolinium chelates and folic acid ligands through “click chemistry”. This macromolecular contrast agent presented high relaxivity relative to small molecule contrast agents and exhibited negligible toxicity estimated in vitro and in vivo. MRI measurements on tumor cells and tissue showed obvious targeting specificity. Moreover, a prominent positive contrast effect and a considerable time window for imaging were achieved at tumor location after tumor-bearing mice were intravenously injected with this macromolecular contrast agent. These promising results demonstrate the potential of hyperbranched poly(glycerol) as a T1 macromolecular contrast agent for tumor-targeted MRI.

The regulation of RNA interference (RNAi) could be a powerful method for the study of temporal and dose dependent effects of gene expression. In this study, we designed the hepatitis delta virus (HDV) ribozyme with an embedded theophylline aptamer as the sensor domain and the pri-miRNA of endogenous gene Bcl-2 as the effector domain to engineer an RNAi-regulatory device in MCF-7 cells. The system allowed us to control gene expression by adding theophylline into the culture media in a dose dependent fashion. This is the pioneering application of ribozyme switches to activate RNAi for modulating endogenous genes in mammalian cells. The platform sets the stage for investigations of other endogenous genes that regulate various biological functions such as differentiation, cell division or cell death, and provides a promising interface with other universal RNAi-based decision-making circuits that operate in mammalian cells. It can be used to study more genes associated with cancer and screen for potential drug targets for gene therapy.

Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM−1 s−1) relative to Gd-DTPA (4.25 mM−1 s−1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA.

•We obtained new aptamer probes for renal cell carcinoma (RCC) by using cell-SELEX only after 12 rounds of selection.•The obtained aptamer W786-1 binds specifically against target cells with the dissociation constant of 9.4 ± 2.0 nM.•The minimized 48-mer aptamer W786-1S showed considerable affinity to target cells.•The aptamers of W786-1 and W786-1S remain good binding affinity and excellent selectivity under physiological condition.Renal cell carcinoma (RCC) is the most common form of kidney cancer with poor prognosis. Early diagnosis of RCC would significantly improve patient prognosis and quality of life. In this work, we developed new aptamer probes for RCC by using cell-SELEX (systematic evolution of ligands by exponential enrichment) only after 12 rounds of selection, in which a clear cell renal cell carcinoma (ccRCC) cell line 786-O was used as target cell, and embryonic kidney cell line 293T as negative control cell. The selected aptamers were subjected to flow cytometry and laser confocal fluorescence microscopy to evaluate their binding affinity and selectivity. The dissociation constant Kd values of four selected aptamers are all in the nanomolar range. Aptamer W786-1 with the best binding affinity and a Kd value of 9.4 ± 2.0 nM was further optimized and its truncated sequence W786-1S showed considerable affinity to 786-O cells. The proteinase and temperature treatment experiment indicated that W786-1 could recognize the target 786-O cells through surface proteins, and remain good binding affinity and excellent selectivity under physiological conditions. Therefore, on the basis of its excellent targeting properties and functional versatility, W786-1 holds great potential to be used as a molecular probe for identifying and targeting RCC.Download high-res image (317KB)Download full-size image

Correction for ‘Hyperbranched poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging in vivo’ by Yi Cao, et al., Polym. Chem., 2017, DOI: 10.1039/c6py01819j.

A G-quadruplex-based fluorescent biosensor for highly sensitive detection of barium ion (Ba2+) was constructed for the first time. In the absence of Ba2+, the G-quadruplex-specific fluorescence ligand N-methyl mesoporphyrin IX (NMM) remained weakly fluorescent when coexisted with a single-stranded G-quadruplex sequence AGRO100. Upon addition of Ba2+, AGRO100 was folded into G-quadruplex structures with the aid of Ba2+, which bound with NMM by stacking forces and significantly enhanced its fluorescence. The maximum fluorescence intensity of NMM was increased by ca. 22-fold in response to 1 μM Ba2+. This simple method exhibites a good linear relationship in the range of 0–600 nM with the detection limit of 4 nM. The detection method is turn-on, fast, economic, high in signal-to-noise ratio and free of participation of toxic organic solvents, demonstrating its great potential for on-site and real-time Ba2+ detection.

Contrast agents with high efficiency and safety are excellent candidates as magnetic resonance imaging probes. Herein, a multi-arm star-branched polymer was prepared by conjugating oligolysine onto a rigid hyperbranched poly(amido amine) core via click chemistry, followed by covalent modification with Gd chelate and folic acid (FA-OLL-g-HBPAMAM-DTPA-Gd). This multi-arm star-branched polymer contrast agent exhibited much higher longitudinal relaxivity (r1 = 13.34 mM−1 s−1) as compared to a commercial contrast agent (Gd-DTPA, r1 = 4.2 mM−1 s−1). No obvious histological toxicity was observed from histological assessment, which illustrated that FA-OLL-g-HBPAMAM-DTPA-Gd exhibited excellent biocompatibility. Both in vitro and in vivo MRI studies showed that the macromolecular contrast agent provided better signal contrast enhancement and presented obvious target specificity to KB xenografts with a sufficient time window for MRI scanning; moreover, this multi-arm star-branched mCA has great potential for developing sensitive and biocompatible MRI CA with targeting ability.

Gadolinium-based macromolecular contrast agents (CAs) with favorable biocompatibility, targeting specificity, and high relaxivity properties are desired for magnetic resonance imaging (MRI) of tumors. Herein, a novel triblock polymeric micelle based on poly(glycerol) (PG) and poly(ε-caprolactone) (PCL) was designed as a nanocarrier to fabricate a tumor targeted contrast agent (CA). Through conjugating gadolinium chelates and folic acid (FA) molecules to the PG block, a triblock-micelle contrast agent (T-micelle) formed from self-assembly demonstrated a low critical micelle concentration (CMC) of 6 mg L−1 and a hydrodynamic diameter of about 250 nm. Compared with small-molecule CAs, the T-micelle exhibited a higher longitudinal relaxivity (r1) of 14.71 mM−1 s−1. Moreover, the cellular viability assay revealed negligible cytotoxicity, and estimation of targeting capacity showed significant targeting specificity to tumor cells. In addition, MRI on tumor-bearing mice confirmed that the T-micelle could efficiently accumulate at the tumor region through targeting specificity and provide obvious contrast enhancement. Consequently, the T-micelle is a promising gadolinium-based macromolecular CA for tumor diagnosis.

PEGylated poly(aspartate-g-OEI) was developed as a magnetic resonance imaging probe. The PEG–PBLA block copolymer was prepared by the ring-opening polymerization of β-benzyl-L-aspartate N-carboxy-anhydride (BLA-NCA) initiated by the terminal primary amino group of mPEG-NH2, followed by grafting with oligoethylenimine (OEI, Mw = 800) and Gd–DTPA. Compared to Gd–DTPA (4.42 mM−1 s−1), PEG–p(Asp–OEI–DTPA–Gd) exhibited much higher T1 relaxivity (19.03 mM−1 s−1), up to 4.3 times higher than Gd–DTPA. No obvious cytotoxicity was observed from the WST assay and H&E analysis, which illustrated that this macromolecular contrast agent (mCA) exhibited excellent biocompatibility. Folic acid (FA) was further labeled onto the mCA to endow the mCA with targeting ability. During in vivo animal studies, the FA labeled MRI probes showed a significant signal intensity enhancement in the tumor during different time intervals and provided a long and efficient window time for MR examination. These results suggest that such mCAs are excellent candidates as magnetic resonance imaging (MRI) probes with high efficiency and safety.

In this work, a uniform multiscale TiO2 nanorod array is fabricated to provide a “multi-scale interacting platform” for cell capture, which exhibits excellent capture specificity and sensitivity of the target cells after modification with bovine serum albumin (BSA) and DNA aptamer. After studying the capture performance of the BSA-aptamer TiO2 nanorod substrates and other nanostructured substrates, we can conclude that the multisacle TiO2 nanorod substrates could indeed effectively enhance the capture yields of target cancer cells. The capture yield of artificial blood samples on the BSA-aptamer TiO2 nanorod substrates is up to 85%–95%, revealing the potential application of the TiO2 nanorods on efficient and sensitive capture of rare circulating tumor cells.

A near-infrared-driven photoelectrochemical aptasensor was developed as a new method for the detection of the breast cancer cell MCF-7. The upconversion nanoparticles and TiO2/CdTe heterostructure were combined to prepare the film electrode, and the high-affinity aptamer AS1411 was conjugated to the electrode to recognize MCF-7 cells. In this fabrication, the upconversion nanoparticles transferred the near-infrared light to visible light, which could excite the semiconductor to enhance the current response. As a result, the aptasensor revealed good sensitivity and specificity with MCF-7 cell concentrations ranging from 1 × 103 to 1 × 105 cells/mL. The results presented a favorable determination of MCF-7 cells, which was achieved with the help of the upconversion nanoparticles and the photoelectrochemical interface.Keywords: aptamer; cancer cells; photoelectrochemical aptasensor; TiO2/CdTe heterostructure; upconversion nanoparticles

Berberine, a new light-up fluorescence ligand, for i-motif structures has been reported. This interaction enabled the development of label-free DNA-based logic gates in response to input signals.

To develop safe and effective macromolecular MRI contrast agents, a macromolecular contrast agent (mCA) containing biocleavable disulfide bonds in the main chain and oligolysine in the side chain is prepared, and its applicability as a MRI contrast agent is demonstrated both in vitro and in vivo. This brush-like mCA possesses a high T1 relaxivity (11.8 mM–1 s–1), up to 3 times higher than the commercial Gd-DTPA (4.2 mM–1 s–1), along with very low toxicity as determined by WST assay and histological analysis. Meanwhile, the disulfide bond can be broken under appropriate reducing conditions, followed by degradation into small fragments. Furthermore, the mCA is functionalized with folic acid to improve the target specificity. In vivo experiments show that FA-labeled mCA can efficiently enhance the resolution between the tumor and surrounding tissues compared to the mCA without FA. This study may provide helpful insights for the further development of sensitive and biocompatible MRI probes.

A cyanine dye-dimethylindole red containing an extending polymethine chain, a sterically bulky dimethylindole heterocycle and an anionic propylsulfonate substituent on the quinoline ring was found to behave as a high specific light-up G-quadruplex probe in the red-emitting region above 650 nm, especially for parallel G-quadruplex c-myc. The 10 to 70-fold enhancement in the fluorescence quantum yield of dimethylindole red when incubating with G-quadruplexes may benefit more accurate definition of the distribution of G-quadruplexes across the genome.

G-quadruplex DNAzymes are peroxidase-like complexes formed by hemin and DNA G-quadruplexes. Many chemical sensors and biosensors have been developed by using this kind of DNAzymes. T4 polynucleotide kinase (PNK), which catalyzes the transfer of the γ-phosphate from ATP to the 5′-hydroxyl termini of polynucleotides, plays an important role in living systems. To build a simple and convenient method to detect the activity of PNK, a split-to-intact DNAzyme was introduced. For this PNK sensor, G-quadruplex-forming G-rich sequence PS5.M was split into two shorter parts S1OH and S2OH, which hybridized to another sequence, helper DNA. In the presence of T4 PNK, 5'-end of sequence S2OH was phosphorylated to S2P. Then S1OH and S2P were linked by T4 DNA ligase to the intact G-quadruplex, PS5.M. The released PS5.M by exonuclease III formed catalytically active G-quadruplex DNAzyme upon hemin binding which could catalyze the oxidation of 2,2′-azino bis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) by H2O2. Quantitative detection of T4 PNK activity could be achieved by measuring the maximal absorbance of product at 418 nm. The absorbance of the sensing system at 418 nm exhibited a linear relationship with T4 PNK activity in the range of 0.02−0.3 U mL−1 with a detection limit of 0.014 U mL−1 (S/N = 3). The method was further applied to the determination of PNK activity in Hela and HEK 293 cell lines, and good recoveries of 95.6%−105.7% were obtained at three spiked levels.A label-free G-quadruplex DNAzyme biosensor detecting T4 PNK was developed using split-to-intact G-quadruplex DNAzyme conversion by T4 DNA ligase and exonuclease III.

Researchers have never stopped questing contrast agents with high resolution and safety to overcome the drawbacks of small-molecule contrast agents in clinic. Herein, we reported the synthesis of gadolinium-based hyperbranched polylysine (HBPLL-DTPA-Gd), which was prepared by thermal polymerization of l-lysine via one-step polycondensation. After conjugating with folic acid, its potential application as MRI contrast agent was then evaluated. This contrast agent had no obvious cytotoxicity as verified by WST assay and H&E analysis. Compared to Gd(III)-diethylenetriaminepentaacetic acid (Gd-DTPA) (r1 = 4.3 mM–1 s–1), the FA-HBPLL-DTPA-Gd exhibited much higher longitudinal relaxivity value (r1 = 13.44 mM–1 s–1), up to 3 times higher than Gd-DTPA. The FA-HBPLL-DTPA-Gd showed significant signal intensity enhancement in the tumor region at various time points and provided a long time window for MR examination. The results illustrate that FA-HBPLL-DTPA-Gd will be a potential candidate for tumor-targeted MRI.

•DNA aptamers of Cd(II), were successfully isolated, and one was optimized to 30-mer.•This sensor showed excellent selectivity in the presence of various metal ions.•This aptamer-based light-up biosensor is simple, cost-effective and quick-testing.In order to develop a facile, cost-effective and quick-testing light-up biosensor with excellent specificity for cadmium ions (Cd(II)) detection, a modified selection method based on target-induced release of strands was used to isolate aptamers of Cd (II) with high specificity. Circular Dichroism (CD) data confirmed that one of the selected aptamers underwent a distinct conformational change on addition of Cd (II). A biosensor for Cd(II) was developed based on the Cd(II)-induced release of fluorescence-labeled aptamer from complex with a quencher-labeled short complementary sequence. The sensing platform displayed a Cd(II) concentration-dependent increase of fluorescence intensity in the low micromolar range and had an excellent selectivity in the presence of various interfering metal ions. Such biosensor could potentially be used for the detection of Cd(II) in environmental samples.

This review (with 139 refs.) gives a fundamental introduction into the sensors and logic gates based on G-quadruplexes (G4s). G4 characterizes vibrant binding activities and topology diversity, which contribute to the multiple signal output modes (including labeled moieties based on distance changes, label-free outputs by employing fluorescent ligands, G4/hemin DNAzyme with catalyzing activity and colorimetric readout using gold nanoparticles) and versatile design strategies (including target-induced G4 formation/disruption, liberation of blocked G4, split G4 probes, polymerase-assisted amplification and G4/hemin enrichment on sensor surface) of G4s-based methods. Following two important trends in logic gates (application of intelligent detection schemes and logic circuit constructions), specific sections review logic sensors and logic circuits based on G4s with several representative examples. We close this review with conclusions and give a perspective that employment of DNA technologies (such as aptamers, DNA junctions/origami, toehold-mediated strand displacement, enzyme-assisted amplification, metal ion-dependent DNAzymes) and various nanomaterials in G4s-based methods results in quite a large potential in terms of logic detection and construction of logic circuits.

A label-free optical probe was developed for Ca2+ detection based on the aggregation-induced emission property of Au(I)–thiolate complexes. Upon incubation with Ca2+, the Au(I)–cysteine complexes rapidly aggregated through Cys–Ca2+ interaction, resulting in a luminescent emission of the complexes. The label-free probe was low cost, simple in design and fast in response.

Using a guanine-rich sequence (AGRO100) and N-methyl mesoporphyrin IX (NMM), a turn-on and label-free fluorescent Pb2+ sensor with high sensitivity and low background fluorescence was presented as a representative of five turn-on sensing systems.

A label-free, fluorescence light-up detection method for T4 polynucleotide kinase activity has been developed using the split-to-intact G-quadruplex strategy.

A novel photoelectrochemical (PEC) biosensor was fabricated based on N-doped TiO2 for the detection of Hg2+ through the quenching of photogenerated electrons. The N-doped TiO2 was synthesized by a sol–gel method with urea and tetrabutyl titanate as the N and Ti sources. Compared with the undoped TiO2, the N-doped TiO2 showed an enhanced photocurrent response under visible light (λ > 420 nm). The sensing surface was functionalized with 5′-amino-modified T-rich oligonucleotides. The photoelectrochemical biosensor bound Hg2+ on the surface by a highly specific T–Hg2+–T recognition. Hg2+ on the surface of the N-doped TiO2 film withdrew the photogenerated electrons and decreased the recorded current signal. The dynamic linear range for Hg2+ has been determined to be as low as 2–6 μM.

A label-free fluorescence K+ assay was developed using riboflavin, a new G-quadruplex ligand, and a G-quadruplex sequence (PW17).

Interestingly, the glutathione capped Au-nanoclusters presented here showed a unique optical performance compared with their homological AuNPs with larger size. The luminescence intensity of the AuNCs could be enhanced due to the formation of aggregates. The AuNCs were then employed as a visual probe for the detection of Pb2+ based on the aggregation-induced emission enhancement (AIEE) property of the AuNCs. When the luminous glutathione capped AuNCs probes encountered Pb2+ ions, they rapidly formed aggregates through GSH–Pb2+ interaction in 1 minute, resulting in an enhanced luminescence intensity. The enhanced luminescence intensities showed a linear dependence on the concentrations of Pb2+ with satisfactory selectivity towards 12 kinds of divalent metal ions. More importantly, the probe can also be used for on-site testing to inspect Pb2+ contamination by using a portable UV flashlight.

By employing two-dimensional and water-soluble graphene oxide (GO), a turn-on sensor was developed for the label-free detection of Zn2+ based on Zn2+-induced G-quadruplex (G4) formation. Indicated using the G4-binding ligand thiazole orange (TO), the enhanced fluorescent signal could be generated only when the guanine-rich DNA was excluded from the surface of GO due to the formation of a G4 induced by Zn2+. The results have shown that the method can be utilized for the detection of Zn2+ in a linear range from 0–30 μM with a detection limit of 0.71 μM. The real sample testing conducted in serum samples demonstrated its practical potential in biological analysis.

This study reported the development of a p–n heterojunction photoelectrochemical biosensor using a G-quadruplex as the recognition system. The n-type ZnO nanorods and p-type BiOI nanoflakes were combined to form the heterostructure by in situ growth of BiOI attributed to a simple impregnating-hydroxylation method. This simple p–n heterojunction fabrication method could facilitate the development of rapid and sensitive visible light activated PEC sensors. In this study, the ZnO/BiOI photoelectrode showed a rapid photocurrent decrease in the presence of Pb2+ due to the electron withdrawing effect of hemin which bound with the G-quadruplex/Pb2+ complex. This PEC biosensor exhibited a good response following the concentration of Pb2+ in the range from 10 to 100 μM.

The decreasing photocurrent from photoinduced electron transfer by the formation of a G-quadruplex/hemin complex in the presence of K+ was utilized as a sensing signal for developing a novel label-free photoelectrochemical detection method.

An N719 dye labeled short DNA chain is introduced onto the surface of a TiO2 photoelectrode by hybridizing with a pre-immobilized thrombin aptamer to enhance the photocurrent response. After incubating with thrombin, both the dye labeled chain releasing from the photoelectrode and the bound thrombin blocking the electron transfer resulted in a decreased photocurrent.

A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

A novel naked-eye distinguishable nanosensor based on phosphorylation triggered poly-nanoparticle assembly strategy has been designed for detecting T4 PNK activity. This colorimetric sensor exhibits conveniently homogeneous operation with simple, sensitive and easily scalable properties.

This paper presents a microchip that isolates and enriches target-binding single-stranded DNA (ssDNA) from a randomized DNA mixture using a combination of solid-phase extraction and electrophoresis. Strands of ssDNA in a randomized mixture are captured via specific binding onto target-functionalized microbeads in a microchamber. The strands are further separated from impurities and enriched on-chip via electrophoresis. The microchip consists of two microchambers that are connected by a channel filled with agarose gel. In the isolation chamber, beads functionalized with human immunoglobulin E (IgE) are retained by a weir structure. An integrated heater elevates the temperature in the chamber to elute desired ssDNA from the beads, and electrophoretic transport of the DNA through the gel to the second chamber is accomplished by applying an electric potential difference between the two chambers. Experimental results show that ssDNA expressing binding affinity to IgE was captured and enriched from a sample of ssDNA with random sequences, demonstrating the potential of the microchip to enhance the sensitivity of ssDNA detection methods in dilute and complex biological samples.

A label-free optical probe was developed for Ca2+ detection based on the aggregation-induced emission property of Au(I)–thiolate complexes. Upon incubation with Ca2+, the Au(I)–cysteine complexes rapidly aggregated through Cys–Ca2+ interaction, resulting in a luminescent emission of the complexes. The label-free probe was low cost, simple in design and fast in response.

Gadolinium-based nanoscale magnetic resonance imaging (MRI) contrast agents (CAs) have gained significant momentum as a promising nanoplatform for detecting tumor tissue in medical diagnosis, due to their favorable capability of enhancing the longitudinal relaxivity (r1) of individual gadolinium ions, delivering to the region of interest a large number of gadolinium ions, and incorporating different functionalities. This mini-review highlights the latest developments and applications, and simultaneously gives some perspectives for their future development.

We report a specific light-up fluorescent probe for i-motif DNA for the first time. Compared with the previously reported probes, neutral red could selectively interact with an i-motif and show a significant increase in its fluorescence. This feature makes it advantageous for designing label-free fluorescent sensing systems.

PEGylated poly(aspartate-g-OEI) was developed as a magnetic resonance imaging probe. The PEG–PBLA block copolymer was prepared by the ring-opening polymerization of β-benzyl-L-aspartate N-carboxy-anhydride (BLA-NCA) initiated by the terminal primary amino group of mPEG-NH2, followed by grafting with oligoethylenimine (OEI, Mw = 800) and Gd–DTPA. Compared to Gd–DTPA (4.42 mM−1 s−1), PEG–p(Asp–OEI–DTPA–Gd) exhibited much higher T1 relaxivity (19.03 mM−1 s−1), up to 4.3 times higher than Gd–DTPA. No obvious cytotoxicity was observed from the WST assay and H&E analysis, which illustrated that this macromolecular contrast agent (mCA) exhibited excellent biocompatibility. Folic acid (FA) was further labeled onto the mCA to endow the mCA with targeting ability. During in vivo animal studies, the FA labeled MRI probes showed a significant signal intensity enhancement in the tumor during different time intervals and provided a long and efficient window time for MR examination. These results suggest that such mCAs are excellent candidates as magnetic resonance imaging (MRI) probes with high efficiency and safety.

An N719 dye labeled short DNA chain is introduced onto the surface of a TiO2 photoelectrode by hybridizing with a pre-immobilized thrombin aptamer to enhance the photocurrent response. After incubating with thrombin, both the dye labeled chain releasing from the photoelectrode and the bound thrombin blocking the electron transfer resulted in a decreased photocurrent.

By employing two-dimensional and water-soluble graphene oxide (GO), a turn-on sensor was developed for the label-free detection of Zn2+ based on Zn2+-induced G-quadruplex (G4) formation. Indicated using the G4-binding ligand thiazole orange (TO), the enhanced fluorescent signal could be generated only when the guanine-rich DNA was excluded from the surface of GO due to the formation of a G4 induced by Zn2+. The results have shown that the method can be utilized for the detection of Zn2+ in a linear range from 0–30 μM with a detection limit of 0.71 μM. The real sample testing conducted in serum samples demonstrated its practical potential in biological analysis.

This study reported the development of a p–n heterojunction photoelectrochemical biosensor using a G-quadruplex as the recognition system. The n-type ZnO nanorods and p-type BiOI nanoflakes were combined to form the heterostructure by in situ growth of BiOI attributed to a simple impregnating-hydroxylation method. This simple p–n heterojunction fabrication method could facilitate the development of rapid and sensitive visible light activated PEC sensors. In this study, the ZnO/BiOI photoelectrode showed a rapid photocurrent decrease in the presence of Pb2+ due to the electron withdrawing effect of hemin which bound with the G-quadruplex/Pb2+ complex. This PEC biosensor exhibited a good response following the concentration of Pb2+ in the range from 10 to 100 μM.

Berberine, a new light-up fluorescence ligand, for i-motif structures has been reported. This interaction enabled the development of label-free DNA-based logic gates in response to input signals.

Using a guanine-rich sequence (AGRO100) and N-methyl mesoporphyrin IX (NMM), a turn-on and label-free fluorescent Pb2+ sensor with high sensitivity and low background fluorescence was presented as a representative of five turn-on sensing systems.

Macromolecular contrast agents (CAs) labeled with targeting molecules are gaining remarkable interest as promising materials overcoming the defects of small-molecule CAs. Designed on the basis of biocompatible poly(glycerol) (PG), a linear macromolecular contrast agent (CA) was synthesized with a composition of PG as a backbone and partial hydroxyl connected with gadolinium labeled poly(L-lysine) dendrons, where folic acid was also conjugated. This linear CA exhibited higher relaxivity (7.04 mM−1 S−1) relative to Magnevist® (3.98 mM−1 S−1), and showed negligible toxicity determined by WST assay and histological analysis. In vitro and in vivo magnetic resonance imaging (MRI) measurements presented obvious target specificity to KB cells and tumor. Moreover, high signal enhancement was observed in the tumor region at various time points after intravenous injection to ensure the long time window for imaging. All the findings make it an attractive candidate for tumor-targeted MRI CAs.

Contrast agents with high efficiency and safety are excellent candidates as magnetic resonance imaging probes. Herein, a multi-arm star-branched polymer was prepared by conjugating oligolysine onto a rigid hyperbranched poly(amido amine) core via click chemistry, followed by covalent modification with Gd chelate and folic acid (FA-OLL-g-HBPAMAM-DTPA-Gd). This multi-arm star-branched polymer contrast agent exhibited much higher longitudinal relaxivity (r1 = 13.34 mM−1 s−1) as compared to a commercial contrast agent (Gd-DTPA, r1 = 4.2 mM−1 s−1). No obvious histological toxicity was observed from histological assessment, which illustrated that FA-OLL-g-HBPAMAM-DTPA-Gd exhibited excellent biocompatibility. Both in vitro and in vivo MRI studies showed that the macromolecular contrast agent provided better signal contrast enhancement and presented obvious target specificity to KB xenografts with a sufficient time window for MRI scanning; moreover, this multi-arm star-branched mCA has great potential for developing sensitive and biocompatible MRI CA with targeting ability.