Artificial hyperthermia is an emerging technique to induce apoptotic cancer cell death. However, achieving effective hyperthermic apoptosis is often difficult, as cells typically acquire resistance to thermal stress. With the aid of sequential irradiation, highly integrated nanoassemblies based on reduced graphene oxide–ZnO nanoparticles–hyaluronic acid (rGo-ZnO-HA) can serve as a multi-synergistic platform for targeted high-performance apoptotic cancer therapy. The surface engineering of ZnO/graphene hybrid with multifunctional HA biomacromolecules simultaneously confers the system colloidal stability, biocompatibility, and a cancer cell targeting ability. After receptor-mediated endocytosis, enzyme-mediated fluorescence activation helps track cellular uptake and provides truly molecular imaging. Furthermore, the reactive oxygen species (ROS) generated by ZnO/rGo under light illumination can effectively sensitize cancer cells to the subsequent NIR laser-induced apoptotic hyperthermia. In particular, photo modulation of cellular ROS to sensitize cells provides a novel approach to increase the efficacy of hyperthermic apoptosis. These findings suggest that a powerful apoptotic therapeutic platform could be achieved based on the multi-synergistic platform.

A facile one-pot synthesis of fluorescent AuNCs by using ovalbumin-CpG oligodeoxynucleotides (ODNs) conjugates as the templates, which can elicit specific immunological responses, is demonstrated. Through dual-delivery of protein antigen and CpG ODNs, the as-prepared AuNCs can act as smart self-vaccines to assist in generation of high immunostimulatory activity while simultaneously act as an imaging agent. The AuNCs-based vaccines are not thought to have not been reported so far, making this platform the first example of the usage of AuNCs as effective vaccines. Furthermore, compared with the antigen, the immunostimulatory activity of the as-prepared AuNCs can not only be retained, but also can be effectively enhanced. These findings suggest the AuNCs-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.

Graphene, a one-atom-thick two-dimensional (2D) layer of sp²-bonded carbon, has received worldwide attention owing to its extraordinary physical and chemical properties. Recently, great efforts have been devoted to explore potential applications of graphene and its oxide in life science, especially in disease-related diagnostics, near-Infrared (NIR) phototherapy and imaging. Here we will introduce recent advances and new horizons in this area, and focus on the rising progress on NIR photothermal therapy for cancer and Alzheimer's disease (AD), human telomerase detection, stem cell proliferation and differentiation on graphene substrate, diagnosis of cancer cell and related biomarkers, drug/nucleotide/peptide delivery and cell imaging, which have not been comprehensively reviewed. We hope to provide an outlook to the applications of graphene and its oxide, especially on the new horizons in this field, and inspire broader interests across various disciplines.

Metal ions have been demonstrated to participate in the pathology of Alzheimer's disease (AD): amyloid-β peptide (Aβ) aggregation and formation of neurotoxic reactive oxygen species (ROS), such as H₂O₂. Metal chelator can block ROS formation and inhibit metal induced Aβ aggregation. Metal-ion chelation therapy as a compelling treatment for AD has been extensively studied. However, most chelators are not suitable for AD treatment because of their poor permeability of the blood–brain barrier and their limited ability to differentiate toxic metals associated with Aβ plaques from those associated with normal metal homeostasis. Here, a novel dual-responsive “caged metal chelator” release system based on gold nanocage (AuNC) for AD treatment is reported. Since arylboronic ester is redox- and thermal-sensitive, phenylboronic acid-functionalized AuNC can serve as an efficient delivery system for H₂O₂-responsive controlled release of metal chelator. The release can be further enhanced through remote control with NIR light because of the high near-infrared absorbance of AuNC. The smart system can effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ-related toxicity. In light of these advantages, this design provides new insights into noninvasive remote control with NIR to improve therapeutic efficacy for treatment of Alzheimer's disease.

Herein, a pH stimuli-responsive vehicle for intracellular drug delivery using CeO₂ capped mesoporous silica nanoparticles (MSN) is reported. β-Cyclodextrin-modified CeO₂ nanoparticles could cap onto ferrocene-functionalized mesoporous silica through host–guest interactions. After internalization into A549 cells by a lysosomal pathway, the ferrocenyl moieties are oxidized to ferrocenium ions by CeO₂ lids, which could trigger the uncapping of the CeO₂ and cause the drugs release. Because of the pH-dependent toxicity, the CeO₂ here behaves as a multi-purpose entity that not only acts as a lid but also exhibits a synergistic antitumor effect on cancer cells. Meanwhile, the cell protective effect of CeO₂ nanoparticles alone is demonstrated, which ensures that the dissolved CeO₂ nanoparticles can be non-toxic to normal cells.

In this paper, we present a facile strategy to synthesize hyaluronic acid (HA) conjugated mesoporous silica nanoparticles (MSP) for targeted enzyme responsive drug delivery, in which the anchored HA polysaccharides not only act as capping agents but also as targeting ligands without the need of additional modification. The nanoconjugates possess many attractive features including chemical simplicity, high colloidal stability, good biocompatibility, cell-targeting ability, and precise cargo release, making them promising agents for biomedical applications. As a proof-of-concept demonstration, the nanoconjugates are shown to release cargoes from the interior pores of MSPs upon HA degradation in response to hyaluronidase-1 (Hyal-1). Moreover, after receptor-mediated endocytosis into cancer cells, the anchored HA was degraded into small fragments, facilitating the release of drugs to kill the cancer cells. Overall, we envision that this system might open the door to a new generation of carrier system for site-selective, controlled-release delivery of anticancer drugs.

Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near-infrared (NIR)-regulated hydrophobic drug-delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin-loaded AuMP-polyethylene glycol-folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote-controlled hydrophobic drug-delivery system with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR-controlled, targeted drug-delivery method would promote the development of high-performance hydrophobic anticancer drug-delivery system in future clinical applications.

Herein, we report a new kind of highly fluorescent probe for Cu²⁺ sensing generated by hydrothermal treatment of graphene quantum dots (GQDs). After hydrothermal treatment in ammonia, the greenish-yellow fluorescent GQDs (gGQDs) with a low quantum yield (QY, 2.5 %) are converted to amino-functionalized GQDs (afGQDs) with a high QY (16.4 %). Due to the fact that Cu²⁺ ions have a higher binding affinity and faster chelating kinetics with N and O on the surface of afGQDs than other transition-metal ions, the selectivity of afGQDs for Cu²⁺ is much higher than that of gGQDs. Furthermore, afGQDs are biocompatible and eco-friendly, and the afGQDs with a positive charge can be easily taken up by cells, which makes it possible to sense Cu²⁺ in living cells. The strategy presented here is simple in design, economical, and offers a “mix-and-detect” protocol without dye-modified oligonucleotides or complex chemical modification.

A facile, economic and green one-step hydrothermal synthesis route using dopamine as source towards photoluminescent carbon nanoparticles (CNPs) is proposed. The as-prepared CNPs have an average size about 3.8 nm. The emission spectra of the CNPs are broad, ranging from approximately 380 (purple) to approximately 525 nm (green), depending on the excitation wavelengths. Due to the favorable optical properties, the CNPs can readily enter into A549 cells and has been used for multicolor biolabeling and bioimaging. Most importantly, the as-prepared CNPs contain distinctive catechol groups on their surfaces. Due to the special response of catechol groups to Fe³⁺ ions, we further demonstrate that such wholly new CNPs can serve as a very effective fluorescent sensing platform for label-free sensitive and selective detection of Fe³⁺ ions and dopamine with a detection limit as low as 0.32 μM and 68 nM, respectively. The new “mix-and-detect” strategy is simple, green, and exhibits high sensitivity and selectivity. The present method was also applied to the determination of Fe³⁺ ions in real water samples and dopamine in human urine and serum samples successfully.

Metal ions play important roles in amyloid aggregation and neurotoxicity. Metal-ion chelation therapy has been used in clinical trials for Alzheimer's disease (AD) treatment. However, clinical trial studies have shown that long-term use of metal chelator can cause adverse side effect, subacute myelo-optic neuropathy. Nanoparticle engineering processes have become promising approaches for efficiently drugs delivery. A series of modified mesoporous silica nanoparticles (MSNs) using redox, pH, competitive binding, light, and enzyme as actuators have been demonstrated. Recently, significant advances in sensing oxidative stress have been made by taking advantage of specific chemistry between cellular oxidants such as H₂O₂. Here we report a biocompatible delivery platform by using H₂O₂ responsive controlled-release system to realize target delivery of AD therapeutic metal chelator. The advantage of this novel strategy is that metal chelator can only be released by the increased levels of H₂O₂, thus, it would not interfere with the healthy metal homeostasis and can overcome strong side effect of metal chelator after long-term use. By taking advantage of the good biocompatibility, cellular uptake properties, and efficient intracellular release of metal chelators, the delivery system is promising for future in vivo controlled-release biomedical applications.

A DNA-encoding strategy is reported for the programmable regulation of the fluorescence properties of silver nanoclusters (AgNCs). By taking advantage of the DNA-encoding strategy, aqueous AgNCs were used as signal transducers to convert DNA inputs into fluorescence outputs for the construction of various DNA-based logic gates (AND, OR, INHIBIT, XOR, NOR, XNOR, NAND, and a sequential logic gate). Moreover, a biomolecular keypad that was capable of constructing crossword puzzles was also fabricated. These AgNC-based logic systems showed several advantages, including a simple transducer-introduction strategy, universal design, and biocompatible operation. In addition, this proof of concept opens the door to a new generation of signal transducer materials and provides a general route to versatile biomolecular logic devices for practical applications.

In recent years, colorimetric biosensing has attracted much attention because of its low cost, simplicity, and practicality. Since color changes can be read out by the naked eye, colorimetric biosensing does not require expensive or sophisticated instrumentation and may be applied to field analysis and point-of-care diagnosis. For transformation of the detection events into color changes, a number of smart materials have been developed, including gold nanoparticles, magnetic nanoparticles, cerium oxide nanoparticles, carbon nanotubes, graphene oxide, and conjugated polymers. Here, we focus on recent developments in colorimetric biosensing using these smart materials. Along with introducing the mechanisms of color changes based on different smart materials, we concentrate on the design of biosensing assays and their potential applications in biomedical diagnosis and environmental monitoring.

A label-free, enzyme-responsive nanosystem that uses a DNA/single-walled carbon nanotube (SWNT) assembly as the substrate is demonstrated for the sensitive, universal detection of restriction and nonrestriction endonucleases as well as methyltransferases in a homogeneous solution on the basis of light scattering (LS) of carbon nanotubes. This protocol is based on the different binding affinities of SWNTs to single- and double-stranded DNA. This difference can lead to different LS signals that can be used for the detection of nuclease cleavage activity. The assay only requires a label-free oligonucleotide probe, significantly reducing the typical cost. The LS technique and the use of a nuclease-specific oligonucleotide probe impart extraordinarily high sensitivity and selectivity. This light scattering assay is universal and label-free with a detection limit of 5 × 10⁻⁶ U μL⁻¹ for S1 nuclease, 1 × 10⁻⁴ U μL⁻¹ for EcoRI endonuclease, and 1 × 10⁻² U μL⁻¹ for EcoRI methylase. In principle, this assay can be used to detect any kind of nuclease by simply changing the DNA sequences of the specific probe.

In this work, a unique, highly sensitive and selective fluorescence turn-on approach for cysteine detection using an ensemble of graphene oxide (GO) and metallized DNA is reported. The method is based on the extraordinarily high quenching efficiency of GO and the specific interaction between cysteine and metallized DNA via robust Ag–S bonds. In the presence of GO, the dye-labeled single-stranded DNA shows weak fluorescence, while it exhibits a dramatic fluorescence increase upon the formation of the double helix through the “activated” metallized DNA by cysteine. In addition, the protocol shows excellent selectivity for cysteine over various other amino acids found in proteins. Importantly, by exploring GO–DNA interactions and the thiol-mediated DNA hybridization, our sensing system can also be utilized to design the “OR” and “INHIBIT” logic gates using cysteine and DNA as inputs. To the author's knowledge, this method is the first example of combining GO and DNA metallization to fabricate a turn-on fluorescent sensor for cysteine and logic gates.

Single-walled carbon nanotubes (SWNTs) have received much attention in nanotechnology because of their potential applications in molecular electronics, field-emission devices, biomedical engineering, and biosensors. Carbon nanotubes as gene and drug delivery vectors or as “building blocks” in nano-/microelectronic devices has been successfully explored. However, since SWNTs lack chemical recognition, SWNT-based electronic devices and sensors are strictly related to the development of a bottom-up self-assembly technique. Here we present an example of using DNA duplex-based protons (H⁺) as a fuel to control reversible assembly of SWNTs without generation of waste duplex products that poison DNA-based systems.

Traditional dye-doped fluorescent graphene oxide (GO) reveals a low quantum yield and a short life expectancy. Herein, red-luminescent silica-coated Eu³⁺ complex nanoparticles were synthesized and covalently coupled to GO nanosheets by means of a carbodiimide-mediated amidation process. SEM and TEM studies demonstrated successful attachment of the silica-coated Eu³⁺ complex nanoparticles onto the GO surface. Spectroscopic studies showed that the GO–nanoparticle conjugates exhibit strong luminescence, long lifetimes, as well as good photostability, which suggests that this new type of luminescent nanomaterial has the potential for highly sensitive time-resolved fluorescence cyto- and histochemistry imaging.

Chiral molecular recognition of human telomeric DNA is important for rational drug design and developing structural probes of G-quadruplexes. Here we report that a chiral supramolecular complex can selectively induce human telomeric G-quadruplex formation and discriminate different G-quadruplex sequences under salt-deficient conditions studied by circular dichroism (CD), UV meltings, stopped-flow spectroscopy, fluorescence resonance energy transfer, enzyme cleavage, and gel electrophoresis. P-enantiomer induced G-quadruplex formation is fast and does not require a large excess of P enantiomer. More importantly, this chiral compound induces loop sequence-dependent G-quadruplex formation.

A robust and photoresponsive DNA network has been designed and constructed from branched DNA and molecular glue. The molecular glue is photoswitchable and can specifically bind to G–G mismatched double-stranded DNA. The assembly process can be reversibly controlled by manipulating the wavelength of light. The approach is flexible, allowing tuning of the size, morphology as well as the cavity of the network by variation of the molar ratio and the isotropic/anisotropic character of the branched building blocks. The assembled architectures are versatile and heat tolerant. These properties should allow the use of the network in further applications.

Cyclin A₂ is a prognostic indicator in early-stage cancer. However, since most of peptide-protein bindings do not produce an easily measurable output signal, this severely hinders homogeneous detection of protein using peptide as detection probe. Cyclin A₂ can be detected as low as 0.6 μM using a well-known p21^(WAF-1) consensus senquence for a specific cyclin A₂ binding motif, which is incorporated into a Tb³⁺ chelating macrocycle by chemical modification at the N-terminus of CMB. Herein, a simple, ultra-sensitive, and selective signal-on fluorescence assay is developed for detection of a prognostic indicator in early-stage cancer, cyclin A₂. Graphene oxide (GO) is even superior to SWNTs for cyclin A₂ detection. The direct detection limit using graphene oxide is 0.5 nM, 10-fold better than using SWNTs, and 1200-fold better than the latest reported value of 0.6 μM using the Tb³⁺ chelating macrocycle modified p21^(WAF-1) peptide.

Cyclin A₂ is a prognostic indicator in early-stage cancer. However, since most of peptide-protein bindings do not produce an easily measurable output signal, this severely hinders homogeneous detection of protein using peptide as detection probe. Cyclin A₂ can be detected as low as 0.6 μM using a well-known p21^(WAF-1) consensus senquence for a specific cyclin A₂ binding motif, which is incorporated into a Tb³⁺ chelating macrocycle by chemical modification at the N-terminus of CMB. Herein, a simple, ultra-sensitive, and selective signal-on fluorescence assay is developed for detection of a prognostic indicator in early-stage cancer, cyclin A₂. Graphene oxide (GO) is even superior to SWNTs for cyclin A₂ detection. The direct detection limit using graphene oxide is 0.5 nM, 10-fold better than using SWNTs, and 1200-fold better than the latest reported value of 0.6 μM using the Tb³⁺ chelating macrocycle modified p21^(WAF-1) peptide.

Here we report a reusable DNA single-walled carbon nanotube (SWNT)-based fluorescent sensor for highly sensitive and selective detection of Ag⁺ and cysteine (Cys) in aqueous solution. SWNTs can effectively quench the fluorescence of dye-labeled single-stranded DNA due to their strong π–π stacking interactions. However, upon incubation with Ag⁺, Ag⁺ can induce stable duplex formation mediated by C–Ag⁺–C (C=cytosine) coordination chemistry, which has been further confirmed by DNA melting studies. This weakens the interactions between DNA and SWNTs, and thus activates the sensor fluorescence. On the other hand, because Cys is a strong Ag⁺ binder, it can remove Ag⁺ from C–Ag⁺–C base pairs and deactivates the sensor fluorescence by rewrapping the dye-labeled oligonucleotides around the SWNT. In this way, the fluorescence signal-on and signal-off of a DNA/SWNT sensor can be used to detect aqueous Ag⁺ and Cys, respectively. This sensing platform exhibits high sensitivity and selectivity toward Ag⁺ and Cys versus other metal ions and the other 19 natural amino acids, with a limit of detection of 1 nM for Ag⁺ and 9.5 nM for Cys. Based on these results, we have constructed a reusable fluorescent sensor by using the covalent-linked SWNT–DNA conjugates according to the same sensing mechanism. There is no report on the use of SWNT–DNA assays for the detection of Ag⁺ and Cys. This assay is simple, effective, and reusable, and can in principle be used to detect other metal ions by substituting C–C base pairs with other native or artificial bases that selectively bind to other metal ions.

Cyclin A₂ plays critical role in DNA replication, transcription, and cell cycle regulation. Its overexpression has been detected and related to many types of cancers including leukemia, suggesting that suppression of cyclin A₂ would be an attractive strategy to prevent tumor progression. Herein, we apply functionalized single wall carbon nanotubes (f-SWNTs) to carry small interfering RNA (siRNA) into K562 cells and determine whether inhibition of cyclin A₂ would be a potential therapeutic target for chronic myelogenous leukemia. The results show functionalized SWNTs can facilitate the coupling of siRNA specifically targeting human cyclin A₂ to form cyclin A₂ siRNA–f-SWNTs complexes. These functionalized SWNTs readily enter K562 cells, resulting in suppression of cyclin A₂ expression. We demonstrate that depletion of cyclin A₂ in this manner inhibits cell proliferation and promotes apoptosis, and cyclin A₂ can serve as a novel therapeutic target. siRNA against cyclin A₂ delivered by functionalized single wall carbon nanotubes may be a useful therapeutic strategy for chronic myelogenous leukemia cells. This would provide new insights on additional therapeutic options for chronic myelogenous leukemia beyond chemotherapy in light of increasing multidrug resistance.

The natural occurrence of the human telomeric G-quadruplex or i-motif in vivo has not been demonstrated and the biological effects of the induction of these structures need to be clarified. Intracellular environments are highly crowded with various biomolecules and in vitro studies under molecular-crowding conditions will provide important information on how biomolecules behave in cells. Here we report that cell-mimic crowding can increase i-motif stability at acid pH and cause dehydration. However, crowding can not induce i-motif formation at physiological pH. Intriguingly, single-walled carbon nanotubes (SWNTs) can drive i-motif formation under cell-mimic crowding conditions and cause more water to be released. To our knowledge, there is no report to show how SWNTs can influence DNA under cell-mimic crowding conditions. Our results indicate that SWNTs may have the potential to modulate the structure of human telomeric DNA in vivo, like DNA B–A transitions and B–Z changes on SWNTs in live cells, which demonstrates potential for drug design and cancer therapy.