Graphitic nanocapsules are emerging nanomaterials which are gaining popularity along with the development of carbon nanomaterials. Their unique physical and chemical properties, as well as good biocompatibility, make them desirable agents for biomedical and bioanalytical applications. Through rational design, integrating graphitic nanocapsules with other materials provides them with additional properties which make them versatile nanoplatforms for bioanalysis. In this feature article, we present the use and performance of graphitic nanocapsules in a variety of bioanalytical applications. Based on their chemical properties, the specific merits and limitations of magnetic, hollow, and noble metal encapsulated graphitic nanocapsules are discussed. Detection, multi-modal imaging, and therapeutic applications are included. Future directions and potential solutions for further biomedical applications are also suggested.

Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core–shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through π–π interactions, a useful tool for cancer-targeted cellular imaging and therapy. Moreover, such a stable and intrinsic fluorescence effect of the AuNR@carbon enabled simultaneous tracking of released therapeutic molecules and nanocarriers under thermo-chemotherapy. The AuNR@carbons had high surface areas and stable shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.

With their unique optical properties and distinct Raman signatures, graphitic nanomaterials can serve as substrates for surface-enhanced Raman spectroscopy (SERS) or provide signal amplification for bioanalysis and detection. However, a relatively weak Raman signal has limited further biomedical applications. This has been addressed by encapsulating gold nanorods (AuNRs) in a thin graphitic shell to form gold graphitic nanocapsules. This step improves plasmon resonance, which enhances Raman intensity, and has the potential for integrating two-photon luminescence (TPL) imaging capability. However, changing the morphology of gold graphitic nanocapsules such that high quality and stability are achieved remains a challenge. To address this task, we herein report a confinement chemical vapor deposition (CVD) method to prepare the construction of AuNR-encapsulated graphitic nanocapsules with these properties. Specifically, through morphological modulation, we (1) achieved higher plasmon resonance with near-IR incident light, thus achieving greater Raman intensity, and (2) successfully integrated two-photon luminescence dual-modal (Raman/TPL) bioimaging capabilities. Cancer-cell-specific aptamers were further modified on the AuNR@G graphitic surface through simple, but strong, π–π interactions to achieve imaging selectivity through differential cancer cell recognition.

Various interferences from measurement conditions and substrate inhomogeneity are well-known confounding factors for poor reproducibility, which is a challenge in surface-enhanced Raman scattering (SERS) quantification. To address these issues, novel substrates and versatile internal standards have been designed and the repeatability is improved to some degree. However, these internal standards are either complex or unstable enough to resist harsh environments such as acid and oxidation. Graphene-isolated-Au-nanocrystal (GIAN) has unique properties and been applied for cell multimodal imaging and chemotherapy but not for SERS quantification analysis yet. Herein, we chose GIANs to improve the accuracy of SERS analysis. GIAN integrates the SERS effect and internal standard into a simple nanoparticle and is proved to be an ideal platform for SERS analysis given its superior properties: (1) chemical stability, it remains stable in strong acid and oxidation, even mimic bioenvironment; (2) a simple core–shell structure, with a thin graphitic shell which is not only a protector that avoiding inner Au catalysis unnecessary reaction but also an internal standard to eliminate the interference during the Raman detections; (3) the big-Π structure can absorb target molecule thus achieve an enrichment effect and quench background fluorescence. Laser power, focus, and substrate fluctuations as well as coexist substance interferences were investigated and the accuracy was improved greatly with the introduction of 2D band internal standard in Raman silent region with less background. Moreover, GIAN was applied for crystal violet determination directly on fish muscle and scale, which was rapid and convenient without complex extraction process. All these results indicate GIAN is an optimum choice for SERS analysis in complex systems.

Elucidating the endocytosis and metabolism of nanoparticles in cells could improve the diagnostic sensitivity and therapeutic efficiency. In this work, we explore the cellular uptake mechanism of a biocompatible nanocrystal nanostructure, graphene-isolated-Au-nanocrystals (GIANs), by monitoring the intrinsic Raman and two-photon luminescence signals of GIANs in live cells. Aptamers functionalized on the GIAN nanostructure through simple, but strong, π–π interactions entered the cells through a clathrin-dependent pathway, while unmodified GIANs mainly entered the cells through a caveolae-mediated endocytosis pathway. Thus, it can be concluded that the mechanism of cellular uptake in these graphene-isolated-Au-nanocrystal nanostructures is determined by the presence or absence of aptamer modification.

Graphitic nanomaterials have unique, strong, and stable Raman vibrations that have been widely applied in chemistry and biomedicine. However, utilizing them as internal standards (ISs) to improve the accuracy of surface-enhanced Raman spectroscopy (SERS) analysis has not been attempted. Herein, we report the design of a unique IS nanostructure consisting of a large number of gold nanoparticles (AuNPs) decorated on multilayered graphitic magnetic nanocapsules (AGNs) to quantify the analyte and eliminate the problems associated with traditional ISs. The AGNs demonstrated a unique Raman band from the graphitic component, which was localized in the Raman silent region of the biomolecules, making them an ideal IS for quantitative Raman analysis without any background interference. The IS signal from the AGNs also indicated superior stability, even under harsh conditions. With the enhancement of the decorated AuNPs, the AGN nanostructures greatly improved the quantitative accuracy of SERS, in particular the exclusion of quantitative errors resulting from collection loss and non-uniform distribution of the analytes. The AGNs were further utilized for cell staining and Raman imaging, and they showed great promise for applications in biomedicine.

Targeted drug delivery is poised to improve cancer therapy, for which synthetic DNA can serve as targeting ligands (for example, aptamers) or drug nanocarriers. Inspired by natural DNA adducts, we report synthetic drug-DNA adducts (DDAs) for targeted anticancer drug delivery. Multiple copies of anthracycline drugs were site specifically (on deoxyguanosine) conjugated on each DNA, enabling programmable design of DNA and drugs for DDA preparation. DDAs were nuclease-resistant and stable for storage, yet gradually released drugs at physiological temperature. DDAs maintained DNA functionalities, including hybridization-mediated DNA nanoadduct formation and aptamer-mediated target recognition and targeted drug delivery into cancer cells. In a tumor xenograft mouse model, doxorubicin-aptamer adducts significantly inhibited target tumor growth while reducing the side effects. Using histopathological analysis and in situ immunohistochemical analysis of caspase-3 cleavage in mouse tumor and heart, DDAs were confirmed to have a potent antitumor efficacy while reducing tissue deformation and apoptosis in the heart, thus providing a new therapeutic avenue to prevent cardiomyopathy, the most dangerous side effect of doxorubicin leading to heart failure. Overall, DDAs are promising for scale-up production and clinical application in targeted anticancer drug delivery.

Many one-photon fluorescence-based theranostic nanosystems have been developed for simultaneous therapeutic intervention/monitoring for various types of cancers. However, for early diagnosis of cancer, two-photon fluorescence microscopy (TPFM) can realize deep-tissue imaging with higher spatial resolution. In this study, we first report a multiple functional nanoprobe for contrast-enhanced bimodal cellular imaging and targeted therapy. Components of the nanoprobe include (1) two-photon dye-doped mesoporous silica nanoparticles (TPD-MSNs); (2) MnO2 nanosheets that act as a (i) gatekeeper for TPD-MSNs, (ii) quencher for TP fluorescence, and (iii) contrast agent for MRI; (3) cancer cell-targeting aptamers. Guided by aptamers, TPD-MSNs are rapidly internalized into the target cells. Next, intracellular glutathione reduces MnO2 to Mn2+ ions, resulting in contrast-enhanced TP fluorescence and magnetic resonance signal for cellular imaging. Meanwhile, preloaded doxorubicin and Chlorin e6 are released for chemotherapy and photodynamic therapy, respectively, with a synergistic effect and significantly enhanced therapeutic efficacy.

In this work, we fabricated a monodisperse nanocomposite by coating gold nanorods (AuNRs) with a layer of biocompatible, stable carbon, obtaining AuNR@Carbon core–shell nanocapsules, which without any functionalization could be used as a molecule loading material due to its high surface areas. In this system, the AuNR core had a high-absorption cross section for conversion of near-infrared light to heat, which could be explored for local hyperthermia. The carbon shell, which was biocompatible and stable even under concentrated acidic and alkaline conditions, was able to adsorb molecules with π–π interactions or electrostatic interactions. In comparison with AuNR@SiO2, AuNR@Carbon nanocapsules demonstrate the following merits: (1) simple and green synthesis method, (2) far more stable with respect to high-temperature stability and (3) larger molecule loading capacity, which indicate great potential in the biomedical applications.利用水热法获得了稳定且生物相容性好的金纳米棒-碳纳米囊材料(AuNR@Carbons),并考察了其分子装载能力。因其具有较大的比表面积和较多的官能团,AuNR@Carbons不用任何修饰就可以作为负载分子的材料。在这种碳纳米囊结构中,具有较大吸收截面的金纳米棒核能将近红外光转化成热用于局部的热疗,而生物相容性良好的碳纳米壳层保护了金纳米棒的热转换性能,并显示了很高的酸碱稳定性。此外,碳纳米壳层还使AuNR@Carbons具有很强的吸附能力,可以通过π-π堆积或静电作用吸附各种分子。跟AuNR@SiO2相比,AuNR@Carbons有以下优势:(1)合成方法简单、绿色;(2)高的热稳定性;(3)大的分子装载能力,这都显示了金纳米棒-碳纳米囊在生物医学应用上的巨大潜力。

In this work, we fabricate an efficient and stable photocatalyst system which has superior recyclability even under concentrated acidic conditions. The photocatalyst is prepared by assembling magnetic graphitic nanocapsules, titania (TiO2) and graphene oxide (GO) into a complex system through π-π stacking and electrostatic interactions. Such catalytic complex demonstrates very high stability. Even after dispersal into a concentrated acidic solution for one month, this photocatalyst could still be recycled and maintain its catalytic activity. With methyl orange as the model molecule, the photocatalyst was demonstrated to rapidly decompose the molecules with very high photocatalytic activity under both concentrated acidic and neutral condition. Moreover, this photocatalyst retains approximately 100 wt% of its original photocatalytic activity even after multiple experimental runs, of magnetic recycling. Finally, using different samples from natural water sources and different dyes, this GO/magnetic graphitic nanocapsule/TiO2 system also demonstrates its high efficiency and recyclability for practical application.

Noble metals, especially gold, have been widely used in plasmon resonance applications. Although silver has a larger optical cross section and lower cost than gold, it has attracted much less attention because of its easy corrosion, thereby degrading plasmonic signals and limiting its applications. To circumvent this problem, we report the facile synthesis of superstable AgCu@graphene (ACG) nanoparticles (NPs). The growth of several layers of graphene onto the surface of AgCu alloy NPs effectively protects the Ag surface from contamination, even in the presence of hydrogen peroxide, hydrogen sulfide, and nitric acid. The ACG NPs have been utilized to enhance the unique Raman signals from the graphitic shell, making ACG an ideal candidate for cell labeling, rapid Raman imaging, and SERS detection. ACG is further functionalized with alkyne-polyethylene glycol, which has strong Raman vibrations in the Raman-silent region of the cell, leading to more accurate colocalization inside cells. In sum, this work provides a simple approach to fabricate corrosion-resistant, water-soluble, and graphene-protected AgCu NPs having a strong surface plasmon resonance effect suitable for sensing and imaging.

Based on their unique advantages, increasing interest has been shown in the use of aptamers as target ligands for specific cancer cell recognition and targeted cancer therapy. Recently, the development of aptamer-conjugated nanomaterials has offered new therapeutic opportunities for cancer treatment with better efficacy and lower toxicity. We highlight some of the promising classes of aptamer-conjugated nanomaterials for the specific recognition of cancer cells and targeted cancer therapy. Recent developments in the use of novel strategies that enable sensitive and selective cancer cell recognition are introduced. In addition to targeted drug delivery for chemotherapy, we also review how aptamer-conjugated nanomaterials are being incorporated into emerging technologies with significant improvement in efficiency and selectivity in cancer treatment.

We have synthesized a nanostructure with a platinum (Pt) nanocrystal core and a few-layer graphene shell. This graphene-encapsulated Pt nanocrystal (GPN) was fabricated through a simple chemical vapor deposition (CVD) method. After investigating the electrocatalytic activities of GPNs, their ability to act as a relatively good fuel cell catalyst was confirmed. Furthermore, to further improve their catalytic activity, a plasma-assisted nitrogen doping method was developed, and the nitrogen-doped graphene-encapsulated Pt nanocrystal (N-GPN) also demonstrated efficient electroactivities, in fact much higher than those reported for conventional Pt–graphene composite catalysts due to their small particle diameter, uniform size distribution, sufficient graphene–Pt contact, and new generation of activation sites after nitrogen doping. This simple and efficient approach could also be extended to the preparation of other alloy nanocrystals coated with a graphene shell for electrocatalytic or electrochemical sensor applications.

An azobenzene-containing surfactant was synthesized for the phase transfer of α-cyclodextrin (α-CD)-capped gold nanoparticles between water and toluene phases by host–guest chemistry. With the use of the photoisomerization of azobenzene, the reversible phase transfer of gold nanoparticles was realized by irradiation with UV and visible light. Furthermore, the phase transfer scheme was applied for the quenching of a reaction catalyzed by gold nanoparticles, as well as the recovery and recycling of the gold nanoparticles from aqueous solutions. This work will have significant impact on materials transfer and recovery in catalysis and biotechnological applications.Keywords: azobenzene; cyclodextrin; host−guest systems; phase transfer; photoresponsive systems

●This paper developed a method of synthesizing hollow graphitic nanocapsules (HGN).●HGNs were used as efficient electrode materials for sensitive, selective and reproducible hydrogen peroxide detection.●HGNs could be utilized as three-dimensional matrices to effectively immobilize enzymes, proteins and small molecules.●A reagentless amperometric biosensor was fabricated by simple coimmobilization of methylene blue and horseradish peroxidase on the HGN-coated electrode.Carbon nanomaterials are typically used in electrochemical biosensing applications for their unique properties. We report a hollow graphitic nanocapsule (HGN) utilized as an efficient electrode material for sensitive hydrogen peroxide detection. Methylene blue (MB) molecules could be efficiently adsorbed on the HGN surfaces, and this adsorption capability remained very stable under different pH regimes. HGNs were used as three-dimensional matrices for coimmobilization of MB electron mediators and horseradish peroxidase (HRP) to build an HGN–HRP–MB reagentless amperometric sensing platform to detect hydrogen peroxide. This simple HGN–HRP–MB complex demonstrated very sensitive and selective hydrogen peroxide detection capability, as well as high reproducibility and stability. The HGNs could also be utilized as matrices for immobilization of other enzymes, proteins or small molecules and for different biomedical applications.

Graphite-coated, highly magnetic FeCo core–shell nanoparticles were synthesized by a chemical vapor deposition method and solubilized in aqueous solution through a unique polymer mixture modification, which significantly improved the biocompatibility and stability of the magnetic nanoparticles (MNPs). Such functionalized MNPs were proven to be very stable in different conditions which would be significant for biological applications. Cell staining, manipulation, enrichment, and detection were developed with these MNPs. Under external magnetic manipulation, the MNP-stained cells exhibited directed motions. Moreover, MNPs were printed on substrates to modulate the magnetic field distribution on the surface. Capture and detection of sparse populations of cancer cells spiked into whole blood has been explored in a microarray fashion. Cancer cells from hundreds down to only two were able to be simply and efficiently detected from 1 mL of whole blood on the MNP microarray chips. Interestingly, the cells captured through the MNP microarray still showed viability and adhered to the MNP spots after incubation, which could be utilized for cancer cell detection, localized growth, and proliferation.Keywords: cells detection; graphite; magnetic nanoparticle; microarray; polymer modification

In this review, we summarize recent progress in the development of single-walled carbon nanotubes (SWNTs) as optical materials for biosensing applications. First, as optical labels, we discuss the use of SWNTs in Raman-based protein detection. Strong and simple resonance Raman spectroscopy of SWNTs opens up a method of protein microarray with detection sensitivity down to femtomolar range. Also, tunable isotopic SWNT-Raman signature enables the simultaneous detection of multiple analytes in complex fluids. Second, the photoluminescence properties of SWNTs are also explored. We examine fluorescence biosensors that integrate the quenching property of SWNTs and the recognition property of functional nucleic acids. Particularly, SWNTs are established as an efficient signal transduction substrate in different biosensing systems, including the detection of specific proteins and DNA sequences, regulation of singlet oxygen generation and label-free fluorescence assays, and all have exhibited very high selectivity and sensitivity.

We have synthesized a nanostructure with a platinum (Pt) nanocrystal core and a few-layer graphene shell. This graphene-encapsulated Pt nanocrystal (GPN) was fabricated through a simple chemical vapor deposition (CVD) method. After investigating the electrocatalytic activities of GPNs, their ability to act as a relatively good fuel cell catalyst was confirmed. Furthermore, to further improve their catalytic activity, a plasma-assisted nitrogen doping method was developed, and the nitrogen-doped graphene-encapsulated Pt nanocrystal (N-GPN) also demonstrated efficient electroactivities, in fact much higher than those reported for conventional Pt–graphene composite catalysts due to their small particle diameter, uniform size distribution, sufficient graphene–Pt contact, and new generation of activation sites after nitrogen doping. This simple and efficient approach could also be extended to the preparation of other alloy nanocrystals coated with a graphene shell for electrocatalytic or electrochemical sensor applications.