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SCIENCE CHINA Chemistry, Volume 61, Issue 10: 1214-1226(2018) https://doi.org/10.1007/s11426-018-9294-9

Recent advancements in 2D nanomaterials for cancer therapy

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  • ReceivedApr 17, 2018
  • AcceptedMay 24, 2018
  • PublishedSep 3, 2018

Abstract

Since mechanical exfoliation of graphene in 2004, unprecedented scientific and technological advances have been achieved in the development of two-dimensional (2D) nanomaterials. These 2D nanomaterials exhibit various unique mechanical, physical and chemical properties on account of their ultrathin thickness, which are highly desirable for many applications such as catalysis, optoelectronics, energy storage/conversion, as well as disease diagnosis and therapeutics. In this review, we summarized recent progress on the design and fabrication of functional 2D nanomaterials capable of being applied for the cancer treatment including drug delivery, photodynamic therapy, and photothermal therapy. Their anticancer mechanisms were discussed in detail, and the related safety concerns were analyzed based on current research developments. This review is expected to provide an insight in the field of 2D nanostructured materials for anticancer applications.


Funded by

the Singapore Academic Research Fund(RG121/16,RG11/17,RG114/17)

the Singapore National Research Foundation Investigatorship(NRF-NRFI2018-03)


Acknowledgment

This work was supported by the Singapore Academic Research Fund (RG121/16, RG11/17, RG114/17) and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03).


Interest statement

The authors declare that they have no conflict of interest.


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  • Scheme 1

    Representative 2D nanomaterials and associated anticancer mechanisms (color online).

  • Figure 1

    Schematic illustration about the conjugation of cypate onto graphene oxide via PEG. The photothermal conversion efficiency of the hybrid nanosystem was enhanced by the reabsorption of cypate fluorescence on the graphene oxide nanosheet through pH-activated FRET [15] (color online).

  • Figure 2

    Schematic illustration for the structure and PTT of gold nanoparticle-deposited graphene oxide nanosheets. Gold nanoparticles were deposited to both sides of graphene oxide via hydrophobic, hydrogen bonding, and electrostatic interactions. The strong surface plasmon coupling significantly enhances the photothermal efficiency under NIR light irradiation. MSC=mesenchymal stem cell; AuNP=gold nanoparticles [17] (color online).

  • Figure 3

    Preparation and therapeutic mechanism of the PEGylated Ru-modified reduced graphene oxide sheets (rGO-Ru-PEG) [42] (color online).

  • Figure 4

    Schematic illustration of the mechanism for the reoxygenation-enhanced PDT with upconversion nanoparticle-deposited MnO2 nanosheets. The decomposition of the MnO2 substrates was triggered by intratumoral acidic pH and excessive H2O2, resulting in the generation of a large amount of oxygen for PDT [44] (color online).

  • Figure 5

    Schematic representation for the tumor penetration of the nanocarrier and the NIR light-controlled release mechanism of DTX from the nanocarrier. The photothermal heating could gasify the loaded PFH to rupture the tumor spheroids, facilitating the tumor-specific drug deposition across the barriers [54] (color online).

  • Figure 6

    Triple combination of PDT, PTT, and chemotherapy with black phosphorus-based nanosystem. Black phosphorus could release ROS under light irradiation at 660 nm and generate heat under light irradiation at 808 nm. Moreover, the DOX release from the nanocarrier could be initiated by acidic endo/lysosomal pH or NIR light treatment [62] (color online).

  • Table 1   Summary of representative 2D nanomaterial-based systems for PTT

    2D substrate

    Modification

    Photothermal conversion efficiency

    Therapeutic benefit

    Dosage

    Ref.

    Graphene oxide

    6-Arm amine-terminated PEG and cypate

    Higher than pristine graphene oxide or cypate due to FRET

    Enhanced photothermal damage to tumor cells

    32.6 mg kg−1

    [15]

    Graphene oxide

    β-Tricalcium phosphate scaffold

    Comparable to pristine graphene oxide

    Combination of PTT and bone generation capability

    Not applicable

    [16]

    Graphene oxide

    Gold nanoparticles

    Higher than pristine gold nanoparticles and graphene oxide due to surface plasmon coupling

    Enhanced photothermal damage to tumor cells

    7.6 μg per mouse

    [17]

    Black phosphorus quantum dots

    PEG chain

    28.4 %

    High photothermal damage, no apparent cytotoxicity

    Cellular experiment: 50 ppm

    [23]

    Black phosphorus

    nanosheets

    Nile blue dye

    Rapid photothermal heating comparable to pristine black phosphorus sheets

    NIR-guided imaging capability

    100 μg per mouse

    [24]

    MnO2 nanosheets

    Soybean phospholipid

    21.4%

    Good photothermal efficiency, acid and GSH responsive degradability, concurrent magnetic resonance imaging capability

    60 μg per mouse

    [25]

    TixTa1−xSyOz hybrid nanosheets (x=0.71, 0.49, 0.30)

    Lipoic acid-conjugated PEG

    39.2 %

    High photothermal damage, no apparent cytotoxicity

    Cellular experiment: 50 ppm

    [26]

    Molybdenum oxide nanosheets

    PEG

    Excellent heating rate due to high light extinction coefficient

    High photothermal damage, rapid clearance

    20 mg kg−1

    [27,37]

    MoS2 nanosheets

    Poly(7-(4-(acryloyloxy) butoxy)coumarin)-b-poly(N-isopropylacryl-amide)s

    Extinction coefficient:

    14.5 L g−1 cm−1 at 808 nm

    Photothermal heating and concurrent fluorescence imaging

    Not applicable

    [28]

    Gd3+-doped WS2 nanoflakes

    PEG

    Extinction coefficient: 22.6 L g−1 cm−1

    Combining photothermal therapy with magnetic resonance imaging

    20 mg kg−1

    [29]

    MoS2/Cu1.8S

    PEG

    Higher than pristine MoS2 or Cu1.8S due to synergistic interaction

    Potent theranostic capability, allowing concurrent chemotherapy

    100 μg per mouse

    [30]

  • Table 2   Summary of representative PDT systems based on 2D nanomaterials

    2D substrate

    Modification

    Quantum yield

    Therapeutic benefit

    Dosage

    Ref.

    Black phosphorus nanosheets

    None

    0.91

    Good biocompatibility and bioavailability, high ROS generation

    15 μg per mouse

    [40]

    Graphene oxide

    PEGylation, sinoporphyrin sodium

    Not applicable

    Fluorescence imaging guided PDT, higher tumor accumulation efficiency

    2 mg kg−1 on nude mice

    [41]

    Reduced graphene oxide

    PEGylated Ru(II) complex

    0.31 for Ru(II) complex

    Lysosome-targeted imaging capability, combined PTT/PDT

    5 mg kg−1 on nude mice

    [42]

    MnO2 nanosheet

    Silica coated upconversion nanoparticles

    Not applicable

    MnO2-mediated tumor reoxygenation for enhanced PDT efficiency

    1.6 mg per mouse

    [44]

    MnO2 nanosheet

    Titanium oxide-coated upconversion nanoparticles

    Not applicable

    Oxygen replenishment through the decomposition of MnO2 and water splitting with TiO2 coating

    1.6 mg per mouse

    [45]

    MnO2 nanosheet

    Ce6

    Not applicable

    GSH removal by MnO2 to enhance 1O2 yield

    8.7 μg per mouse

    [46]

  • Table 3   Summary of representative 2D nanomaterial-based drug delivery systems

    2D substrate

    Modification

    Delivery cargo

    Therapeutic benefit

    Dosage

    Ref.

    Graphene oxide

    PEGylation

    SN-38

    DOX loading amount at around 10%

    1 mg L−1 for cell experiments

    [48]

    Graphene oxide

    Antibody conjugation

    DOX

    Targeting tumor vasculature

    1.1 mg kg−1

    [49]

    Graphene oxide

    Redox-sheddable hyaluronic acid coating

    DOX

    Tumor-targeted cytoplasmic drug release

    5 mg kg−1

    [50]

    C3N4 nanosheet

    Mesoporous silica coating, deposited with Fe3O4 nanoparticles and modified with iRGD ligands

    DOX

    Tumor targeted pH-sensitive drug release with two-photon imaging capability

    60 μg mL−1 for cell study

    [51]

    Black phosphorus nanosheet

    PEGylation, folic acid

    DOX

    Theranostic capabilities

    7.1 mg kg−1

    [52]

    Black phosphorus nanosheet

    Agarose gel coating

    DOX

    Precise NIR controlled drug release, complete degradability

    500 μg per mouse

    [53]

    Graphene oxide

    Mesoporous silica coating, encapsulation with lipid bilayers, lactoferrin ligands

    Docetaxel and gasified perfluoro-hexane

    Capable of disrupting the tumor spheroids and enhancing the intratumoral drug accumulation

    6 mg kg−1

    [54]

  • Table 4   Summary of representative 2D nanomaterials for combined therapy

    2D substrate

    Therapeutic modality

    Modification

    Therapeutic benefit

    Dosage

    Ref.

    Graphene nanosheet

    PTT, DOX-dependent chemotherapy

    Silica coating, conjugated with targeting ligand IL-13Rα2

    Targeted delivery to glioma cells with controllable drug release

    50 μg mL−1 for cell incubation

    [58]

    MoS2 nanosheet

    PTT, DOX-dependent chemotherapy

    Polymer coating for DOX loading

    pH and NIR tunable drug release

    300 μg mL−1 for cell incubation

    [59]

    Graphene oxide

    PTT, PDT

    Conjugated with folic acid for tumor targeting

    Combining simultaneous PTT/PDT with fluorescence imaging

    8 mg kg−1

    [60]

    Black phosphorus nanosheet

    PTT, PDT

    PEGylation, loaded with rhodamine B

    Theranostic capability

    50 μg per mouse

    [61]

    Black phosphorus nanosheet

    PTT, PDT, chemotherapy

    DOX

    Acidity/photothermal responsive drug release, synergistic therapy, good biocompatibility

    0.5 mg kg−1

    [62]

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