key: cord-0866995-rk89s780
authors: He, Yang; Hu, Chenyan; Li, Zhijia; Wu, Chuan; Zeng, Yuanyuan; Peng, Cheng
title: Multifunctional carbon nanomaterials for diagnostic applications in infectious diseases and tumors
date: 2022-03-05
journal: Mater Today Bio
DOI: 10.1016/j.mtbio.2022.100231
sha: 80b7ca5819b23c6d8d05594777d12d3d5cf6ad12
doc_id: 866995
cord_uid: rk89s780

Infectious diseases (such as Corona Virus Disease 2019) and tumors pose a tremendous challenge to global public health. Early diagnosis of infectious diseases and tumors can lead to effective control and early intervention of the patient's condition. Over the past few decades, carbon nanomaterials (CNs) have attracted widespread attention in different scientific disciplines. In the field of biomedicine, carbon nanotubes, graphene, carbon quantum dots and fullerenes have the ability of improving the accuracy of the diagnosis by the improvement of the diagnostic approaches. Therefore, this review highlights their applications in the diagnosis of infectious diseases and tumors over the past five years. Recent advances in the field of biosensing, bioimaging, and nucleic acid amplification by such CNs are introduced and discussed, emphasizing the importance of their unique properties in infectious disease and tumor diagnosis and the challenges and opportunities that exist for future clinical applications. Although the application of CNs in the diagnosis of several diseases is still at a beginning stage, biosensors, bioimaging technologies and nucleic acid amplification technologies built on CNs represent a new generation of promising diagnostic tools that further support their potential application in infectious disease and tumor diagnosis.

(CQDs) according to the nature of the core structure, carbon precursor, and quantum effect, respectively [63] . CDs possess unique 140 photoluminescence (PL) properties that distinguish them from other CNs and enable the construction of fluorescent probes for 141 optical biosensors and bioimaging. It was confirmed that CDs with graphitic properties were identified to have visible 142 excitation-dependent high fluorescence in the UV to NIR region. Furthermore, CDs have been reported to have two-photon and 143 multi-photon fluorescence emission [64] , enabling promising applications in multi-photon fluorescence imaging. CDs, as well as 144 to other CNs, also have excellent electrocatalytic activity, which makes them potentially useful in the construction of 145 electrochemical materials [65] . Furthermore, their water solubility and biocompatibility are promising thanks to the 146 oxygen-containing functional groups (e.g., hydroxyl and carboxyl groups) that can encapsulate CDs. Compared with 147 semiconductor quantum dots containing heavy metals, the outstanding biocompatibility and chemical inertness of CDs render 148 them more suitable for biomedical applications. Therefore, the application of CDs in disease diagnosis has increased significantly 149 in recent years due to these advantages. These studies explore detection techniques that are more suitable to clinical diagnosis by 150 adjusting the chemical structure of CDs or integrating them with other nanomaterials, such as metal nanoparticles GO and CNTs. (ATP) using C60 modified Au nanoparticles@MoS2 (C60-AuNP@MoS2) composites as signal indicators and p-type PbS QDs as 296 signal quenchers [92] . The photoelectric conversion efficiency of C60 alone is low, whereas the PEC signal of the C60 modified by biomarker for tumors) and insulin (Insulinoma-induced abnormal levels of insulin) with high sensitivity and selectivity using 324 luminol-delabeled nitrogen-doped CNDs (NCNDs) and nano-C60 (the nanoparticles of C60) respectively, to modify the working 325 electrode [98, 99] . 326

In addition to the modification of CNs for their use directly on the electrodes, Yang and coworkers constructed an ECL 327 immunosensor for the detection of prostate-specific antigen (PSA) using AuNPs/GQDs-polyetherimide (PEI)-GO complexes as 328 probes [100] . When PSA is present, a sandwich structure composed of Ab1-GCE//PSA//Ab2-AuNP/GQDs-PEI-GO is formed. 329

The application of a voltage to the electrode resulted in the emission of light by GQDs and PSA is quantified according to this 330 signal (LOD, 0.44 pg mL -1 ). A similar strategy was applied by Qin et al. who detected human chorionic gonadotropin (HCG) 331 (promotion of tumor growth and invasion), a hormone produced by the placenta (LOD, 0.33 μIU mL -1 ), using CQDs-loaded silver 332 nanoparticles (AgCQDs)@polymer nanospheres (PNS)-PEI nanocomplexes as ECL signaling probes [101] . Carbon 333 nanomaterial-based ECL signaling probes can potentially detect relevant biomarkers in spiked human serum samples, indicating 334 their potential use in the diagnosis of infectious diseases and tumors.s. 335

Colorimetric biosensors work thanks to the colorimetric reaction that generates colored compounds and allow the evaluation 338 of the biomarker concentration by comparing or measuring the color shades of the colored solutions. The exceptionally distinctive 339 optical properties of CNs encouraged extensive research to develop these biosensors for the detection of biomarkers. In addition, 340

CNs have a large specific surface area, can load multiple biomolecules, and can protect biomolecules (e.g., nucleic acids or 341 proteins) from enzymatic digestion or degradation by the environment [102,103]. These properties enable the detection of 342 numerous biomarkers, including proteins, DNA and bacteria by colorimetric biosensors based on CNs (Fig. 4a) . A summary of 343 some of the key colorimetric sensing studies on CNs (and their composites) for infectious disease and tumor diagnosis in the last 344 five years is presented in Table S3 . 345 oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) for the absolute quantification of biomarkers according to the degree of color 347 change of the solution (colorless to blue). Xia et al. reported the construction of a selective biosensor for exosomes consisting of 348 the modification of SWCNTs with aptamers to enhance the microperoxidase activity of SWCNTs to further catalyze the oxidation 349 of TMB; the aptamers leave the surface of SWCNTs after binding to the exosomal transmembrane protein CD63, resulting in a 350 dark to light color of the solution (LOD, 5.2 × 10 5 μL -1 ) [104]. On the other hand, the large specific surface area of CNs allows 351 the increase of the loading of other materials with peroxidase-like activity, such as polyoxometalates (POMs) and MnO2, to 352 further enhance the peroxidase activity of the loaded materials for a stable, sensitive and specific detection of biomarkers [e.g., 353

L-cysteine (abnormal levels to cause cancer) and glutathione] [105, 106] . allowing the quantitative detection of E. coli (LOD visible to the naked eye, 10 cells mL -1 ). Unfortunately, the sensor does not 361 work using clinical samples but only using coconut water samples, thus, this principle is a promising research field for a future 362 development of optical sensors suitable for clinical point-of-care (POC) testing. Wei et al. developed a colorimetric and 363 photothermal sensor for the sensitive detection of PSA according to a similar principle of the recognition of the target by aptamers, 364 using GO-modified Fe3O4 NPs as signal probes [109] . The addition of PSA alters the conformation of the aptamer and triggered 365 the detachment of GO/Fe3O4 from the surface of the substrate. Subsequently, the remaining Fe3O4 NPs in the microplate is 366 converted to Prussian blue (PB) NPs, by mixing with potassium ferricyanide, which generated a colorful compound recognizable 367 with the naked eye. Moreover, PB NPs induce an increase in the temperature of the immunoassay solution by NIR laser mL -1 , which is significantly below the threshold of PSA concentration of 4.0 ng mL -1 for the clinical diagnosis of prostate cancer, 370 thus meeting the clinical requirements. 371

Apart from the conventional liquid-phase colorimetric biosensors, colorimetric biosensors based on CNs can also be applied 372 to immunochromatographic analysis and are usually used for the identification of biomarkers by visual inspection (Fig. 4b) . Jia et 373 al. established an assay for the rapid detection of the carcinoembryonic antigen (CEA) in the blood using a composite reporter 374 probe of CNTs/AuNPs conjugated with specific antibodies on cotton thread [110] . Thanks to the CEA immobilized on cotton 375 threads against specific antibodies, the CNTs/AuNP nanocomposite stacking in the test area appears as a ribbon visible with 376 naked-eye allowing the quantification of CEA (linear range, 10-500 ng mL -1 functionalization and extra-high specific surface area. They can be readily functionalized by nanoparticles, small molecule dyes, 452 polymers or biomolecules to acquire specific molecular probes or contrast agents for different bioimaging applications to be 453 significantly at the tumor site with blood circulation (half-life of ~5.6 h). Currently, CNs whose fluorescence is located in the 484 NIR-II window suffer from high absorption, but by utilizing sufficiently bright fluorophores is an effective way to overcome the 485 absorption effect. NIR imaging, a promising imaging technique, has not yet been applied to clinical diagnosis, but the 486 development of imaging reagents with wider emission ranges and greater safety may be the direction of development to enhance 487 NIR-II imaging capabilities. inhibition [137] . A-GQDs were capable of being internalized by human lung cancer A549 cells, resulting in a clear two-photon 498 green fluorescent cell image observed at 750 nm excitation wavelength. In addition, A-GQDs were confirmed to exhibit 499 white-light-activated antimicrobial properties. Despite TPFI imaging based on CNs is still in the early stage of exploration, the 500 current study also indicates that the use of CNs as fluorescent TPFI probes is particularly suitable for in vivo studies of biological 501 structures in the NIR range. 502

nanoparticles as substrates and combined them with alkyne derivatives exhibiting strong Raman signals in the acoustic region of 508 cells (1800-2800 cm -1 ), resulting in a successful application for imaging hypoxic HepG2 cells and tissues (Fig. 5c ) [138] . 509

Hypoxia is a feature of several diseases including cancer. Raman spectroscopy revealed that the signal intensity of 510 hypoxia-incubated HepG2 cells in the 2180-2230 cm -1 channel gradually decreased with decreasing oxygen concentration, and in 511 addition, hypoxia in liver tissue was still detectable at a penetration depth of 600 μm. In another similar work, Huth et al. Wistar rats (Fig. 6a) [147]. PET imaging of 64 Cu@SWCNTs@β-D-glucan revealed that 64 Cu@SWCNTs@β-D-glucan is able to 565 mainly localize into the lung and myocardium. In addition, PET can be combined with optical imaging. 566

Fluorescein-functionalized 64 Cu-C60-PEG-cyclo (Arg-Gly-Asp) peptides (cRGD) are able to target integrin αvβ3, which is 567 involved in angiogenesis, and the biodistribution of integrin αvβ3 in U87MG cells and glioblastomas in mice in vivo can be 568 observed by fluorescence and PET multimodal imaging (Fig. 6b) Tc I and Gd-anchored ultra-small nanographene oxide-PEG ( 99m Tc-usNGO PEG) based on a chelator-free strategy and 570 successfully imaged lymph nodes in normal BALB/c mice in vivo with SPECT/CT and MRI (Fig. 6c) [149] . SPECT/CT imaging 571 is able to detect popliteal lymph nodes, sacral lymph nodes, caudal lymph nodes and mesenteric lymph nodes in mice. Besides, 572 99m Tc-usNGO PEG in MRI also detect the aggregation in the popliteal lymph nodes. 573 PAI is based on laser-generated ultrasound for imaging the lesion site by combining the high penetration depth of ultrasound 574 imaging with the excellent contrast of fluorescence imaging [150, 151] . CNTs produce acoustic waves after 500-700 nm laser target regions characterized by active bone metabolism (Fig. 6d) [153]. Bisphosphonates (BPs) have a high binding affinity for 577 hydroxyapatite (HA) at the site of bone injury or disease. The tail vein injection of SWCNTs-BP-99m Tc in Balb/c mice resulted in 578 PAI displaying clear bone localization, with a rapid clearance in the blood after 1 h, demonstrating the potential of 579

SWCNTs-BP-99m Tc for targeted diagnostic and drug release. Additionally, PAI can be combined with CT to obtain an ideal 580 dual-modality imaging technique that provides spatial, positional, and distribution information of lesions in deep tissues to 581 simultaneously obtain high-resolution pathological images and highly sensitive molecular information on the disease [154] . improves the specificity of error-prone multi-round PCR [160] . GO used in PCR systems promotes the formation of matched 608 primer-template complexes, but inhibits the formation of mismatched primer-template complexes during the PCR, suggesting that 609 the interaction between primers and GO plays an important role. The existing hypothesis suggested that GO can adsorb ssDNA 610 (e.g. primers) through π-π stacking and hydrogen bonding, thereby allowing the matched primer-template complexes to be 611 detached from its surface for subsequent PCR reactions, while the primers remain adsorbed on its surface when mismatched. The 612 above findings encouraged our group to introduce in 2019 GOQDs into the qRT-PCR system to improve its performance [161] . 613

GOQDs can adsorb primers and TaqMan probes by π-π stacking and hydrogen bonding, thereby reducing the background 614 fluorescence intensity of TaqMan probes, reducing the non-specific amplification in PCR reactions and improving the specificity 615 of the detection. This GOQDs-based qRT-PCR can detect DNA sequences of two different lengths (106 bp and 65 bp) with a 616 linear range of 10 4 -10 10 copies μL -1 . Subsequently, GO was further applied to qRT-PCR to establish a GO-based qRT-PCR assay 617 to detect ovarian cancer-associated miRNAs (Fig. 7a) [162]. Our group discovered that the pre-adsorbing of the primers on the 618 GO surface improves the efficiency of PCR amplification by increasing the efficiency of the primer template hybridization and 619 reducing the non-specific amplification, thus increasing the sensitivity of qRT-PCR. The minimum detection limit of the assay is In addition of introducing CNs alone into the qRT-PCR system, several groups have also achieved a sensitive diagnosis of 623 diseases by constructing complexes based on CNs. Kim Most studies have focused only on the potential mechanisms of CNs as PCR enhancers despite the abundance of research 635 devoted to the application of these nanomaterials in improving PCR performance, with few of these studies focusing in PCR 636 techniques directly applied to the detection of nucleic acid biomarkers in patient specimens for clinically relevant diseases. 637

Nonetheless, these studies also provide strong evidence that CNs have the potential to improve the performance of PCR and may 638 be a potential platform for infectious diseases and tumors diagnosis. 639

In addition to the introduction of CNs into PCR systems, several studies explored the utility of CNs in other NAATs. RCA is 641 one of the thermostable NAATs that uses a circular template and a special DNA polymerase (e.g., Phi29) to achieve a targeted with virus-specific antigen/antibody/capture nucleic acid sequences. It is well known that the design and preparation of 677 virus-specific antigen/antibody/capture nucleic acid sequences is a time-consuming and complex procedure, which is detrimental 678 for the prompt diagnosis of emerging infectious diseases. Therefore, the exploitation of biometric elements with simple 679 preparation techniques is a critical challenge, offering a promising research strategy for the early diagnosis of infectious diseases 680 and tumors. 681

In addition, the development of CNs-based diagnostic technologies (especially in the field of biosensing) still suffers from 682 the following problems. First of all, the stability of the established analytical techniques is a salient issue in disease diagnosis that 683 is essential for the potential diagnostic application of CNs. Although the current techniques are often reproducible using standard 684 samples, the standardization of materials remains elusive. Currently established diagnostic techniques are typically stable within a 685 few weeks to one month of a batch [171], but ensuring that a specific amount and structural properties of CNs remain the same 686 from batch to batch is still a challenge. In general, oxygen-containing groups on the surface of CNs increase the aqueous 687 solubility, but the oxidation process also introduces uncertainties into defecting surface areas [172] . The presence of these addition, the different suitability of clinical specimens affects the stability of the analytical techniques. Although most studies 691 measured substances in the samples (e.g., whole blood, serum/plasma, and urine) that may interfere with the detection results The toxicity of CNs is also a specific concern when applied in vivo, especially as contrast agents for in vivo bioimaging. 704

Numerous reports demonstrated that myeloperoxidase in vivo is capable of producing hypochlorite to degrade CNs [174, 175] . 705

Currently, most of the studies on CNs degradation have focused on oxidized CNs owing to their favorable biocompatibility and 706 dispersibility [176] . Nevertheless, depending on the preparation method, CNs in an aggregated state are usually difficult to be 707 completely degraded due to the small area of binding to the enzyme [177] . Furthermore, during the preparation process, 708 multitudes of researchers frequently encapsulate CNs with polymers in pursuit of low toxicity, which further interferes with the 709 interaction between enzymes and CNs [175] . Although related studies proved that CNs can be completely degraded by enzymatic 710 catalysis in vitro, it still seems to be challenging to achieve complete degradation of CNs in living organisms. Accordingly, the 711 potential long-term toxicity and degradation of CNs in organisms remains an ongoing concern. 712 Last but not least, the development of diagnostic technologies based on CNs is still in its infancy. According to the reported on diagnostic technologies developed based on CNs are still at the stage of proof of concept or analysis of a small number of 715 patient samples (<100 samples). The accuracy and methodological stability of these methods when applied to large clinical 716 samples remains to be proven. On the other hand, although many researchers are currently inclined to develop POC testing 717 devices (mainly including various sensing devices), the results of POC testing can only provide clinicians with references for 718 further work and cannot be regarded as a direct basis for diagnosis. In terms of SARS-CoV-2 testing, the final diagnosis still 719 depends on the combination of qRT-PCR results and CT results as diagnostic criteria. Therefore, whether the combined analysis 720 between test results can improve the accuracy of disease diagnosis may be the direction clinicians expect to investigate. 

SARS -beginning to 737 understand a new virus

Middle East respiratory syndrome

A novel coronavirus from patients with pneumonia in China

Detection of SARS-CoV-2 using antibody-antigen 744 interactions with graphene-based nanomechanical resonator sensors

Carbon nanomaterials in oncology: an expanding horizon

Photoluminescence architectures for disease diagnosis: from graphene to thin-layer transition metal 749 dichalcogenides and oxides

Carbon nanomaterials in biological studies and biomedicine

Fluorescent polymer-single-walled carbon nanotube complexes with charged and noncharged dendronized 763 perylene bisimides for bioimaging studies

Multifunctional graphene oxide/iron oxide nanoparticles for 765 magnetic targeted drug delivery dual magnetic resonance/ fluorescence imaging and cancer sensing

Fluorescent and photoacoustic 768 bifunctional probe for the detection of ascorbic acid in biological fluids, living cells and: in vivo

Fluorophore-functionalized 771 graphene oxide with application in cell imaging

Graphene and carbon nanotube-graphene hybrid 774 nanomaterials for human embryonic stem cell culture

Graphene/single-walled carbon nanotube hybrids promoting osteogenic 777 differentiation of mesenchymal stem cells by activating p38 signaling pathway

Gold nanoparticle/graphene oxide 780 hybrid sheets attached on mesenchymal stem cells for effective photothermal cancer therapy

A simple sonochemical approach to fabricate a urea biosensor based on zinc 783 phthalocyanine/graphene oxide/urease bioelectrode

Screen-printed carbon electrodes modified with graphene oxide for 786 the design of a reagent-free NAD + -dependent biosensor array

Colorimetric detection of 789 immunomagnetically captured rare number CTCs using mDNA-wrapped single-walled carbon nanotubes

Biomedical applications of carbon nanomaterials: drug and gene delivery 792 potentials

Carbon and graphene 794 quantum dots: a review on syntheses, characterization, biological and sensing applications for neurotransmitter 795 determination

Functionalized carbon nanomaterials: exploring the interactions with

Caco-2 cells for potential oral drug delivery

Structure and chemistry of graphene oxide in liquid water from first 875 principles

Carbon-based nanomaterials for biomedical applications: a recent study

Whole cell FRET immunosensor based on 879 graphene oxide and graphene dot for Campylobacter jejuni detection

The Distribution and imaging of 99m

Tc-nGO-PEG-FA in human patu8988 tumor-bearing nude mice

Performances of a pristine 885 [Ru(dcbpy)2dppz] 2+ /Rose Bengal dyes co-sensitized fullerene for DNA detection

A photoelectrochemical biosensor based on fullerene with 992 methylene blue as a sensitizer for ultrasensitive DNA detection

p-n-sensitized heterostructure Co3O4/Fullerene with highly 995 efficient photoelectrochemical performance for ultrasensitive DNA detection

Fullerenol as a photoelectrochemical nanoprobe 998 for discrimination and ultrasensitive detection of amplification-free single-stranded DNA

Synthesis of gold nanoparticles@reduced porous graphene-modified 082 ITO electrode for spectroelectrochemical detection of SARS-CoV-2 spike protein

A graphene oxide-gold nanostar 085 hybrid based-paper biosensor for label-free SERS detection of serum bilirubin for diagnosis of jaundice

Graphene oxide-assisted and DNA-modulated SERS of AuCu alloy 088 for the fabrication of apurinic/apyrimidinic endonuclease 1 biosensor

Graphene-based nanomaterials for bioimaging

Preparation, photoluminescence properties and 093 application for in vivo tumor imaging of curcumin derivative-functionalized graphene oxide composite

Fasting-dependent vascular permeability enhancement in brown adipose tissues evidenced by using carbon 106 nanotubes as fluorescent probes

Fluorescence imaging in vivo at wavelengths beyond 1500 nm

Graphene-based nanomaterials for versatile imaging studies

Amino-functionalized nitrogen-doped 113 graphene-quantum-dot-based nanomaterials with nitrogen and amino-functionalized group content dependence for 114 highly efficient two-photon bioimaging

Graphene 116 quantum dots modified with adenine for efficient two-photon bioimaging and white light-activated antibacteria

Nanoconjugates of Ag/Au/Carbon nanotube for alkyne-meditated 119 ratiometric SERS imaging of hypoxia in hepatic ischemia

Single-walled carbon 130 nanotube-loaded doxorubicin and Gd-DTPA for targeted drug delivery and magnetic resonance imaging

A new high-performance 134 gadonanotube-polymer hybrid material for stem cell labeling and tracking by MRI

Single-layer boron-doped graphene quantum dots for 137 contrast-enhanced: in vivo T1-weighted MRI

Activatable core-shell metallofullerene: an efficient 140 nanoplatform for bimodal sensing of glutathione

Laser-assisted in situ synthesis of graphene-based 143 magnetic-responsive hybrids for multimodal imaging-guided chemo/photothermal synergistic therapy

Near-infrared light-mediated photodynamic/photothermal therapy 146 nanoplatform by the assembly of Fe3O4 carbon dots with graphitic black phosphorus quantum dots

Behavior of supramolecular assemblies of radiometal-filled and fluorescent carbon nanocapsules in vitro and in vivo

Positron emission tomography (PET) guided glioblastoma targeting 153 by a fullerene-based nanoplatform with fast renal clearance

Chelator-free conjugation of 99m Tc and Gd 3+ to PEGylated nanographene oxide for dual-modality SPECT/MR 157 imaging of lymph nodes

A review of clinical 160 photoacoustic imaging: current and future trends

Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice

99m Tc-functionalized single-walled carbon nanotubes for bone targeting

Core-shell Pd@Au nanoplates as theranostic 171 agents for in-vivo photoacoustic imaging, CT imaging, and photothermal therapy

Ultrafast 174 synthesis of gold nanosphere cluster coated by graphene quantum dot for active targeting PA/CT imaging and 175 near-infrared laser/pH-triggered chemo-photothermal synergistic tumor therapy

Highly sensitive and multiplexed quantification of mRNA splice 178 variants by the direct ligation of DNA probes at the exon junction and universal PCR amplification

Bioanalytical applications of isothermal nucleic acid amplification techniques

Graphene oxide/nucleic-acid-stabilized silver nanoclusters: 183 Functional hybrid materials for optical aptamer sensing and multiplexed analysis of pathogenic DNAs

Extraction of viral 186 nucleic acids with carbon nanotubes increases SARS-CoV-2 quantitative reverse transcription polymerase chain 187 reaction detection sensitivity

Graphene oxide enhances the specificity of the polymerase chain reaction by 189 modifying primer-template matching

A strategy for preparing non-fluorescent graphene oxide quantum dots as 191 fluorescence quenchers in quantitative real-time PCR

Graphene oxide-based qRT-PCR assay enables the sensitive and 194 specific detection of miRNAs for the screening of ovarian cancer

Effects of graphene oxide-gold nanoparticles nanocomposite on 197 highly sensitive foot-and-mouth disease virus detection

Nanoparticle PCR: nanogold-assisted PCR with 200 enhanced specificity

Size-dependent interactions between Au Nanoparticles and DNA in 202 electrochemical oxidation by metal complexes

Extensible multiplex real-time PCR for rapid bacterial identification 205 with carbon nanotube composite microparticles

Self-assembled DNA nanoflowers triggered by a DNA walker 208 for highly sensitive electrochemical detection of Staphylococcus aureus

ATP mediated rolling circle amplification and opening DNA-gate for drug delivery 211 to cell

Graphene oxide-based suppression of nonspecificity in 213 loop-mediated isothermal amplification enabling the sensitive detection of cyclooxygenase-2 mRNA in colorectal 214 cancer

Combined recombinase polymerase amplification/rkDNA-graphene oxide probing 216 system for detection of SARS-CoV-2

Competitive amperometric immunosensor for determination 219 screen-printed electrodes: a potential rapid and 220 noninvasive screening tool for early diagnosis of urinary tract carcinoma

Improved synthesis of graphene oxide

Clinically accurate diagnosis of Alzheimer's disease via 225 multiplexed sensing of core biomarkers in human plasma

Biodegradation of carbon nanotubes by macrophages

Biodegradation of carbon nanotubes, graphene, and their derivatives

Degradation-by-design: how chemical functionalization enhances the 232 biodegradability and safety of 2D materials

Dispersibility-dependent biodegradation of graphene oxide by myeloperoxidase

Reproduced with permission from ref

MRI of H22 tumor-bearing nude mice treated with GO-PEG-γ-Fe2O3-DOX. The histogram 267 demonstrates the temporal T2 signal of the tumor site acquired by region-of-interest (ROI) analysis. Reproduced with permission 268 from ref