A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics
Abstract
:1. Introduction
- Stealth strategies: nanocarriers can be coated with polymers (e.g. Polyethylene glycol, PEG) to keep them invisible to the immunity system and increase their circulation time;
- Targeting or sensing strategies: nanocarriers can be functionalized with ligands that are recognized by receptors overexpressed in cancer cell tissues;
- Triggering strategies: nanocarriers’ composition can be sensible to stimulus (e.g. pH, temperature changes) and releasing their cargo accordingly.
2. Methods
2.1. Eligibility Criteria
2.2. Information Sources, Search Strategy, Study Selection, and Data Collection Process
2.3. Data Items and Quality Assessment
3. Results
4. Discussion
4.1. Role of Graphene-Based Nanomaterials in Therapy
4.1.1. Overview of the Different Therapeutic Strategies
4.1.2. Critical Comparison of Therapeutic Outcomes
4.2. Role of Graphene-Based Nanomaterials in Diagnostic
4.3. Role of Graphene-Based Nanomaterials in Toxicity
4.4. Pharmaceutical Applications of Graphene-Based Nanomaterials and Clinical Translation Prospects
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Graphene-Based Nanomaterial | Graphene Type | Coating | Theranostic System Size (D or D × T) | Zeta-Potential/ Colloidal Stability in Serum | Proven Graphene Therapeutic Relevance | Proven Graphene Diagnostic Relevance | Ref. |
---|---|---|---|---|---|---|---|
Au@PLA-(PAH/GO)n | GO | 1.5 µm | n.r. | USI (Figure 2) s.e. Au@PLA | [61] | ||
UCNPs-NGO/ZnPc | GO | PEG | ≈ 300 × 1.5 nm (GO) + 40 nm (UCNPs) | n.r. | PTT (Figure 3 and Figure S4) | [85] | |
GO-HA-Ce6 | GO | ≈ 440 nm | n.r. 1 d stability | PTT (Figure 3) s.e. Ce6 | [52] | ||
ICG-GO-FA | GO | PEG-FA | ≈ 200 nm | n.r. 3 h stability | PTT (Figure S3, Figure 2 and Figure 3) s.e. ICG | [86] | |
GO-AuNS | GO | ≈ 0.8 μm | −19 mV 10 days | PTT (Figure 6) s.e. AuNS | [70] | ||
GQD-Cur | GO | ≈ 150 nm (GQD-Cur) 3–6 nm (GQD) | n.r. | PL (Figure 6) | [78] | ||
GO-Abs/Cy7 | GO | 100–600 × 1.2 nm | n.r. | PAT (Figure 3 and Figure 9) s.e. Cy7 | PAI (Figure 3 and Figure 6) s.e. Cy7 | [72] | |
GDH | GO | HA | ≈ 120 nm (GDH) ≈ 30 nm (GO) | n.r. 7 days | PTT (Figure 5a) | [62] | |
PheoA+GO:FA-BSA-c-PheoA | GO | PEG-FA | ≈ 180 nm | ≈ −30 mV n.r. | PTT + PDT (Figure 7 and Figure 9) s.e. Pheo | [47] | |
GO-PEG-ZnS:Mn-DOX | GO | PEG-ZnS:Mn | n.r. | n.r. | PL (Figure 4) s.e. ZnS:Mn | [53] | |
CPGA | GO | PEG | ≈ 230 × 15 nm | ≈ −25 mV 7 d stability | PTT (Figure 3) s.e. Au and Cy5.5 | PAI (Figure 2) FI (Figure 2) s.e. Au | [56] |
GO@Gd-PEG-FA/DOX | GO | PEG-FA | n.r | ≈ −6 mV | PTT (Figure 6) | [75] | |
GO/AuNS-PEG/Ce6 | GO | PEG | ≈ 400 × 18 nm | ≈ −38 mV 1 d stability | PTT (Figure 2b) s.e. AuNS | [87] | |
GO/Bi2Se3/PVP | GO | ≈ 150 nm | ≈ −18 mV (GO) n.r. | PTT (Figure 5d) s.e. Bi2Se3 | [92] | ||
GO/UCNPs ZnFe2O4 | GO | PEG | ≈ 400 nm | ≈ −17 mV n.r. | PTT (Figure 2d) PDT+PTT (Figure 3) s.e. UCNPs | [48] | |
GO/MnWO4/PEG | GO | PEG | ≈ 130 nm | ≈ −26 mV n.r. | PTT (Figure 3) | [5] | |
LOGr-Pc-LHRH | LOGr | PEG | ≈ 80 nm | n.r. n.r. | PTT (Figure 3a and Figure 6b) PDT (Figure 6c) s.e. Pc | [81] | |
GO-DOX | NGO | PEG | ≈ 30 × 6 nm | n.r. | PAI (Figure 5) s.e. Cy 5.5 | [71] | |
ICG-FeCl3@GO | NGO | _ | ≈ 40 nm | n.r. | PTT (Figure 3d) s.e. ICG | [83] | |
GO@Ag-DOX-NGR | NGO | DSPE-PEG-NGR | ≈ 40 nm | −29 mV | PTT (Figure 6) s.e. Ag | [76] | |
GO-PEG-DVDMS | NGO | PEG | ≈ 20.5 × 1.5 nm | n.r. | PTT (Figure 2a, Figure 3a and Figure 3d) s.e. DVDMS | [88] | |
IO/GO-COOH | NGO | OA | ≈ 50 × 20 nm | n.r. | PTT (Figure 5) s.e. IO | MRI (Figure 3) s.e. IO | [60] |
GO-PEG-CysCOOH | NGO | PEG-CysCOOH | < 50 × 2 nm | n.r. 1 d stability | PTT (Figure 2 and Figure 4) s.e. CysCOOH | PAI (Figure 3) s.e. CysCOOH | [73] |
Au@NGO | NGO | ≈ 98 nm | ≈ −28 mV n.r. | SERS (Figure 3) s.e. Au | [68] | ||
NGO-PEG-FA | NGO | PEG-FA | ≈ 100 nm | n.r | PTT (Figure 4, Figure 5, Figure 6 and Figure 7 | FI (Figure 3) | [7] |
NGO-IR-808 | NGO | PEG | ≈ 20–40 × 3 nm | n.r. | PTT (Figure 2, Figure 3 and Figure 7) s.e. IR-808 | FI (Figure 4 and Figure 6) IR-TI (Figure 7) s.e. IR-808 | [67] |
NGO-PEG-ICG/PTX | NGO | PEG-ICG | < 100 × 1 nm | ≈ −30 mV 14 d stability | PTT (Figure 4, Figure S5 and Figure 6) s.e. ICG | FI (Figure 5) s.e. ICG | [91] |
NGO-UCNPs-Ce6 | NGO | OA | ≈ 100 nm (GO)+ 48 nm (UCNPs) | n.r. | PTT (Figure S4, Figure 7 and Figure 8) PDT+PTT (Figure 3, Figure 7 and Figure 8) s.e. UCNPs | [57] | |
UCNP@NGO | NGO | OA | ≈ 100 nm (GO)+ 55 nm (UCNPs) | n.r. | PTT (Figure 2, Figure 4 and Figure 5) s.e. UCNPs | [64] | |
BSA/nano-rGO | rGO | BSA | ≈ 70 nm | ≈ −30 mV 30 d stability | PTT (Figure 3) | PAI (Figure 4 and Figure 5) | [74] |
rGONM-PEG-Cy7-RGD | rGO | PEG | ≈ 61 nm | n.r. | PTT (Figure 2) | [46] | |
rGO-Fe2O3@AuNPs | rGO | NH2-PEG | ≈ 610 nm | −21.1 mV > 5 h | PTT (Figure 3a) s.e. Fe2O3@Au NPs | [50] | |
rGO nanosheets | rGO | HA | ≈ 115 nm | ≈ −60 mV n.r. | PTT (Figure 4a and Figure 5a) s.e. ICG | [69] | |
131I-RGO-PEG | rGO | PEG | ≈ 50 × 3.5 nm | n.r. 7 days | PTT (Figure 2) s.e. 131I | γ-image (Figure 3) s.e. 131I | [51] |
rGO-AuNRVe | rGO | PEG | ≈ 74 nm | n.r. | PTT (Figure 2) s.e. AuNR | PAI (Figure 5) s.e. AuNR | [79] |
anti-EGFR-PEG-rGO@ CPSS-Au-R6G | rGO | PEG-Anti-EGFR | < 200 nm | n.r. | PTT (Figure S5 and Figure 7b) s.e. AuNPs | [6] | |
ICG-PDA-rGO | rGO | PDA | 1–5 μm × 1 nm | n.r. | PTT (Figure 3 and Figure 8) s.e. ICG | PAI (Figure 4 and Figure 6) IR-TI (Figure 7) s.e. ICG | [59] |
rGO-GSPs | rGO | PEG | ≈ 100 nm | n.r. 3 d stability | PTT (Figure 2a and Figure 2b) s.e. AuNPs | PAI (Figure 2d and Figure 2e) s.e. AuNPs | [66] |
rGO-mfHSA | rGO | mfHSA | ≈ 200 nm | −25 mV 2 d stability | PTT (Figure 3c) | [93] | |
FA-PEG-Lip@rGO/Res | rGO | PEG-FA | ≈ 220 nm | ≈ −24 mV 7 d stability | PTT (Figure 7b) | IR-TI (Figure 7a) | [58] |
ArGO | rGO | APGA | ≈ 115 nm | ≈ −38 mV 28 d stability | PTT (Figure 5b and Figure 6a) | IR-TI (Figure 5a) | [77] |
AAP10-pDA/rGO | rGO | pDA | 300 nm × 3.5 nm | n.r. | PTT (Figure 2) s.e. pDA | [90] | |
cGdots | GQDs | ≈ 5 nm | n.r. n.r. | All therapeutic outcomes came from GQDs | All diagnostic outcomes came from GQDs | [45] | |
GQDs | GQDs | 2–6 nm | n.r. | All therapeutic outcomes came from GQDs | All diagnostic outcomes came from GQDs | [44] | |
PLA-PEG-grafted GQDs (f-GQDs) | GQDs | PLA-PEG | ≈ 22 × 1.7 nm | ≈ −4 mV n.r. | PL (Figure 4) | [55] | |
AS1411@GQD | GQDs | ≈ −13 mV n.r. | PTT (Figure 6a and Figure 6b) s.e. AS1411 | [84] | |||
HA-GQD -SiO2 NPs | GQDs | ≈ 40 nm | n.r. | PDT (Figure 6) s.e. HA and SiO2 | [94] | ||
GQDs@Cys-BHC | GQDs | ≈ 5 nm | n.r. | FI (Figure 8) | [82] | ||
Fe3O4@SiO2@GQDs-FA/DOX | GQDs | ≈ 25 nm | ≈ −18 mV n.r. | PL (Figure 3) FI (Figure 5) | [80] | ||
GQD-MSN--DOX | GQDs | 50-80 nm | n.r. | PTT (Figure 6 and Figure 9) | [89] | ||
GQD-PEG-P | GQDs | PEG | 8 × 1 nm | ≈ + 14 mV n.r. | PTT (Figure 3) | FI (Figure 5) | [49] |
DOX@GQD-P-Cy | GQDs | ≈ 15 nm | ≈ −4 mV (w/o) DOX n.r. | FI (Figure 4d–e) s.e. DOX by FRET | [54] | ||
DL-GQD-comp | GQDs | ≈ 220 nm | n.r. | ― | PL (Figure 5) | [63] | |
IR780/GQDs-FA | GQDs | 8.5 × 1.5 nm | n.r. | PTT (Figure 5a and Figure 5b) s.e. IR780 | FI (Figure 6) IR-TI (Figure 7a) s.e. IR780 | [65] | |
SCNA (DOX/GQD) | GQDs | HTPGS | < 5 nm | n.r. 4 h stability | PTT (Figure 5e) | CLSMI (Figure 4) | [8] |
Graphene-Based Nanomaterial | THERAPY | DIAGNOSTIC | Ref. | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Drug, Bioactive, PS, or Gene | Trigger | MHT | PTT PAT | PDT | Sensing/ Targeting | Therapy Guiding | ||||||||||
Optical | Non-Optical | |||||||||||||||
FI, PL | 2PFI or UCLI | IR-TI | Raman, SERS | X-ray | MRI | PET, CT SPECT | PAI | USI | ||||||||
Theranostic strategies of graphene-based nanomaterials containing GO | ||||||||||||||||
Au@PLA-(PAH/GO)n | + | + | + | [61] | ||||||||||||
UCNPs-NGO/ZnPc | ZnPc (PS) | + | + | + | [85] | |||||||||||
GO-HA-Ce6 | Ce6 (PS) | HA | + | + | + | [52] | ||||||||||
ICG-GO-FA | + | FA | + | + | [86] | |||||||||||
GO-AuNS | + | + | [70] | |||||||||||||
GQD-Cur | Cur (Bioactive) | + | [78] | |||||||||||||
GO-Abs/Cy7 | +PAT | Abs | + | [72] | ||||||||||||
GDH | DOX (Drug) | NIR, pH GDH | + | HA | + | + | [62] | |||||||||
PheoA+GO:FA-BSA-c-PheoA | PheoA (PS) | pH | + | + | FA | + | [47] | |||||||||
GO-PEG-ZnS:Mn DOX | DOX (Drug) | pH | + | [53] | ||||||||||||
CPGA | Cy5.5 (PS) | + | + | MMP-14(P) | + | + | + | [56] | ||||||||
GO@Gd-PEG-FA/DOX | DOX (Drug) | + | FA | + | [75] | |||||||||||
GO/AuNS-PEG/Ce6 | Ce6 (PS) | + | + | + | [87] | |||||||||||
GO/Bi2Se3/PVP | + | + | + | + | [92] | |||||||||||
GO/UCNPs ZnFe2O4 | ZnFe2O4 (PS) | + | + | + | + | + | + | + | [48] | |||||||
GO/MnWO4/PEG | DOX (Drug) | NIR, pH | + | + | + | [5] | ||||||||||
LOGr-Pc-LHRH | Pc (PS) | NIR | + | + | + | [81] | ||||||||||
Theranostic strategies of graphene-based nanomaterials containing NGO | ||||||||||||||||
GO-DOX | DOX (Drug) | pH | + | [71] | ||||||||||||
ICG-FeCl3@GO | ICG (PS) | + | + | AGE-Aptamer | + | [83] | ||||||||||
GO@Ag-DOX-NGR | DOX (Drug) | NIR | + | NGR | + | [76] | ||||||||||
GO-PEG-DVDMS | DVDMS (PS) | NIR | + | + | + | [88] | ||||||||||
IO/GO-COOH | + | + | + | [60] | ||||||||||||
GO-PEG-CysCOOH | + | + | + | [73] | ||||||||||||
Au@NGO | DOX (Drug) | + | [68] | |||||||||||||
NGO-PEG-FA | + | + | FA | + | + | [7] | ||||||||||
NGO-IR-808 | IR-808 (PS) | NIR | + | + | BPEI | + | + | [67] | ||||||||
NGO-PEG-ICG/PTX | PTX (Drug) | pH | + | [91] | ||||||||||||
NGO-UCNPs-Ce6 | Ce6 (PS) | + | + | + | [57] | |||||||||||
UCNP@NGO | + | + | + | [64] | ||||||||||||
Theranostic strategies of graphene-based nanomaterials containing rGO | ||||||||||||||||
BSA/nano-rGO | + | + | + | + | [74] | |||||||||||
rGONM-PEG-Cy7 RGD | + | RGD | + | [46] | ||||||||||||
rGO-Fe2O3 @AuNPs | DOX (drug) | NIR Magnetic | + | + | + | [50] | ||||||||||
rGO nanosheets | + | + | [69] | |||||||||||||
131I-rGO-PEG | 131I (Radio- therapy) | NIR | + | + | + | [51] | ||||||||||
rGO-AuNRVe | DOX (drug) | NIR pH | + | + | + | [79] | ||||||||||
anti-EGFR-PEG-rGO@CPSS-Au-R6G | + | Anti-EGFR | + | + | [6] | |||||||||||
ICG-PDA-rGO | + | + | + | [59] | ||||||||||||
rGO-GSPs | + | + | + | [66] | ||||||||||||
rGO-mfHSA | + | + | [93] | |||||||||||||
FA-PEG-Lip@rGO/Res | Res (Bioactive) | + | FA | + | [58] | |||||||||||
ArGO | + | + | [77] | |||||||||||||
AAP10-pDA/rGO | AAP10 (Peptide) | + | + | [90] | ||||||||||||
Theranostic strategies of graphene-based nanomaterials containing GQDs | ||||||||||||||||
cGdots | + | + | + | [45] | ||||||||||||
GQDs | PpIX (PS) | + | + | [44] | ||||||||||||
PLA-PEG-grafted GQDs (f-GQDs) | IP ASODN (Gene) | + | [55] | |||||||||||||
AS1411@GQD | AS1411 (Gene) | NIR | + | AS1411 | + | [84] | ||||||||||
HA-GQD-SiO2 NPs | Hypocrellin (PS) | + | + | [94] | ||||||||||||
GQDs@Cys-BHC | BHC (Bioactive) | pH | + | [82] | ||||||||||||
Fe3O4@SiO2 @GQDs-FA/DOX | DOX (Drug) | pH | FA FRET | + | + | [80] | ||||||||||
GQD-MSN-DOX | DOX (Drug) | + | + | [89] | ||||||||||||
GQD-PEG-P | P (PS) | + | + | + | [49] | |||||||||||
DOX@GQD--P-Cy | DOX (Drug) | Peptide P | FRET | + | [54] | |||||||||||
DL-GQD-comp | DOX (Drug) | pH | HER | + | [63] | |||||||||||
R780/GQDs-FA | + | FA | + | + | [65] | |||||||||||
SCNA (DOX/GQD) | DOX (Drug) | NIR + HTPGS | + | + | + | [8] |
Graphene-Based Nanomaterial (GBNs) | In Vitro | In Vivo | Ref | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Cell Model | Dark Cell Viability [GBNs] (Method) | NIR Laser | Drug or Active, Dose, AL(wt%) | Therapeutic Outcomes [GBNs] (Method) | Animal Model and Dose | Toxicity (Method) | NIR Laser | Drug or Active, Dose, AL(wt%) | Therapeutic Outcomes (Method) | ||
Therapeutic outcomes and toxicity evaluation of graphene-based nanomaterials containing GO | |||||||||||
Au@PLA-(PAH/GO)n | HeLa HUVECs | 90% HUVECs viability with 1000 µg/mL (Trypan blue) | λ = 808 nm P = 6.67 W/cm2 t = 6 min | ― |
| Xenograft mice (HT1080 cells) 20 mg/Kg |
| λ = 808 nm P = 2.23 W/cm2 t = 10 min | ― |
| [61] |
UCNPs-NGO/ZnPc | KB HeLa | >90% with 320 µg/mL (MTT) | - PDT: λ = 630 nm P = 50 mW/cm2 t = n.r. - PTT: λ = 808 nm P = 2 W/cm2 t = 10 min | ZnPc n.r. |
| ― | ― | ― | ― | ― | [85] |
GO-HA-Ce6 | A549 | ≈84% with 1.8 µM Ce6 (CCK-8) | λ = 810 nm P = 4 W/cm2 t = 8 min | ― |
| ― | ― | ― | ― | ― | [52] |
ICG-GO-FA | HeLa | ≈100% with 20 µg/mL (MTT) | λ = 808 nm P = 2 W/cm2 t = 10 min | ― |
| ― | ― | ― | ― | ― | [86] |
GO-AuNS | SKBR-3 MCF-10a | ≈95% in SKBR-3 and MCF-10a with 40 µg/mL (MTT) | λ = 808 P = 0.75 W/cm2 t = 2 | ― |
| ― | ― | ― | ― | ― | [70] |
GQD-Cur | HCT166 | >90% with 100 µg/mL (SRB) | ― | Cur AL ≈ 41% |
| Xenograft mice (HCT166) 10 mg/Kg |
| ― | Cur AL ≈ 41% |
| [78] |
GO-Abs/Cy7 | U87-MG | ≈95% with 42.8 µg/mL (CCK-8) | λ = n.r. P = 0.016W/cm2 t = n.r. | ― |
| Xenograft mice (U87-MG cells) 43.4 µg/mouse |
| λ = 753 nm P = 0.02 W/cm2 t = 1 min | ― |
| [72] |
GDH | MDCK A549 | ≈80–85% MDCK cell viability with 100 µg/mL (MTT) | λ = 670 nm P = 1 W/cm2 t = 5 min | DOX 100 μg/mL AL n.r. |
| Xenograft mice (A549 cells) 2.5 mg/Kg |
| λ = 670 nm P = 1 W/cm2 t = 30 min | DOX n.r. |
| [62] |
PheoA+GO:FA-BSA-c-PheoA | B16F10 MCF-7 | 100% with 0.375 µg/mL (MTT) | λ = 670 nm P = 0.13 W/cm2 t = 10 min | ― |
| Xenograft mice (B16F10 cells) 2 mg/Kg |
| λ = 670 nm P = 0.13 W/cm2 t = 10 min | ― |
| [47] |
GO-PEG-ZnS:Mn-DOX | HeLa; CHO-K1 | 100% with 1000 µg/mL (w/o DOX) (MTT) | ― | DOX 300 μg/mL AL ≈ 10% |
| ― | ― | ― | ― | ― | [53] |
CPGA | SCC7 | ≈70% with 200 µg/mL (MTT) | λ = 808 nm P = 0.3 W/cm2 t = 10 min | ― |
| Xenograft mice (SCC7 cells) 10 mg/Kg |
| λ = 808 nm P = 0.75 W/cm2 t = 10 min | ― |
| [56] |
GO@Gd-PEG-FA/DOX | MCF-7 | ≈85% with 10 µg/mL (w/o DOX) (SRB) | λ = 808 nm P = 2.5 W/cm2 t = 5 min | DOX 10 µg/mL AL≈94% |
| Xenograft mice (S180 cells) 10 mg/Kg |
| λ = 808 nm P = 2 W/cm2 t = 5 min | DOX 5 mg/kg AL ≈ 94% |
| [75] |
GO/AuNS- -PEG/Ce6 | EMT6 | >95% with 100 µg/mL (CCK-8) | λ = 660 nm P = 2 W/cm2 t = 8 min | ― |
| Xenograft mice (EMT6 cells) 10 mg/kg |
| λ = 660 nm P = 3 W/cm2 t = 10 min | ― |
| [87] |
GO/Bi2Se3/ PVP | HeLa | >90% with 75 µg/mL (MTT) | λ = 808 nm P = 0.3 W/cm2 t = 10 min | ― |
| Xenograft mice (HeLa) 0.2 mg/mouse |
| λ = 808 nm P = 0.4 W/cm2 t = 5 min | ― |
| [92] |
GO/UCNPs ZnFe2O4 | HeLa; L929 | 80% with 500 µg/mL (MTT) | λ = 980 nm P = 0.8 W/cm2 t = 15 min | ― |
| Xenograft mice (U14 cells) n.r. |
| λ = 980 nm P = 0.8 W/cm2 t = 15 min | ― |
| [48] |
GO/MnWO4/PEG | 4T1 HUVEC | 90% and 80% (4T1 and HUVEC cell) with 100 µg/mL (MTT) | λ = 808 nm P = 0.6 W/cm2 t = 10 min | DOX 5 µg/mL AL ≈ 55% |
| Xenograft mice (U14 cells) 0.6 mg/mouse |
| λ = 808 nm P = 0.6 W/cm2 t = 10 min | DOX 0.2 mg/mouse AL ≈ 55% |
| [5] |
LOGr-Pc-LHRH | A2780/AD RBC |
| λ = 690 nm P = 0.95W/cm2 t = 15 min | Pc 4 µg/mL |
| Xenograft mice (A2780/AD cells) 1 mg/Kg | ― | ― | ― |
| [81] |
Therapeutic outcomes and toxicity evaluation of graphene-based nanomaterials containing NGO | |||||||||||
GO-DOX | ― | ― | ― | ― | ― | Xenograft mice (H1975 cells) n.r. |
| ― | DOX 8 mg/kg AL = 133% |
| [71] |
ICG-FeCl3@GO | G361 | ― | λ = 785 nm P = 1 W/cm2 t = 20 min | ICG n.r. |
| ― | ― | ― | ― | ― | [83] |
GO@Ag-DOX-NGR | MCF-7 | ≈90% with 10 µg/mL (SRB) | λ = 808 nm P = 2 W/cm2 t = 3 min | DOX 4 µg/mL AL ≈ 82% |
| Xenograft mice (S180) 6.1 mg/Kg |
| λ = 808 nm P = 2 W/cm2 t = 3 min | DOX 5 mg/kg AL ≈ 82% |
| [76] |
GO-PEG-DVDMS | PC9 | ≈70% with 3 µg/mL (MTT) | - PDT: λ = 630 nm P = 3 J/well t = n.r. - PTT: λ = 808 nm P = 1 W/cm2 t = 3 min | DVDMS n.r |
| Xenograft mice (PC9 cells) 1 mg/Kg |
| - PDT: λ = 630 nm 50 J t = n.r. - PTT: λ = 808 nm P = 1 W/cm2 t = 10 min | DVDMS 2 mg/kg |
| [88] |
IO/GO-COOH | HeLa | 95% with [Fe] = 200 µg/mL (MTT) | λ = 808 nm P = 2 W/cm2 t = 5 min | ― |
| Xenograft mice (S180 cells) 37.5 µg /mouse |
| λ = 808 nm P = 1 W/cm2 t = 5 min | ― |
| [60] |
GO-PEG-CysCOOH | 4T1 | ≈100% with 250 µg/mL (MTT) | λ = 808 nm P = 0.5 W/cm2 t = 3 min | ― |
| Xenograft mice (4T1) 450 μg/mouse |
| λ = 808 nm P = 0.5 W/cm2 t = 5 min | ― |
| [73] |
Au@NGO | HeLa cells | ≈80% with 200 µg/mL (MTT) | ― | DOX 25 µg/mL AL ≈ 2% |
| ― | ― | ― | ― | ― | [68] |
NGO-PEG-FA | B16F0 | ≈90% with 75 µg/mL (MTT) |
λ = 808 nm P = 0.32 W/cm2 t = 15 min
λ = 980 nm P = 0.32 W/cm2 t = 18 min | ― |
| Xenograft mice (B16F10 cells) 8 mg/Kg | ― |
λ = 808 n P = 0.25 W/cm t = 8 mi
λ = 980 nm P = 0.25 W/cm2 t = 10 min | ― |
| [7] |
NGO-IR-808 | A549; Lewis lung | Negligible toxicity with 10 µM (CCK-8) | λ = 808 nm P = 2 W/cm2 t = 5 min | ― |
| Xenograft mice (A549; Lewis lung cells) 10 mg/Kg |
| λ = 808 nm P = 1 W/cm2 t = 5 min | ― |
| [67] |
NGO-PEG-ICG/PTX | MG-63 | ≈100% with 200 µg/mL (w/o PTX) (CCK-8) | ― | PTX 100 µg/mL AL ≈ 90% |
| Xenograft mice (MG-63) 10 mg/kg |
| ― | PTX 9 mg/kg AL ≈ 90% |
| [91] |
NGO-UCNPs-Ce6 | HeLa; L929 | >95% with 800 µg/mL (MTT) | λ = 808 nm P = 0.72 W/cm2 t = 10 min | ― |
| Xenograft mice (U14 cells) n.r. |
| λ = 808 nm P = 0.72 W/cm2 t = 10 min | ― |
| [57] |
UCNP@ NGO | 4T1 | >90% with 400 µg/mL (MTT) | λ = 808 nm P = 2 W/cm2 t = 10 min | ― |
| Xenograft mice (4T1 cells) n.r. |
| λ = 808 nm P = 1 W/cm2 t = 5 min | ― |
| [64] |
Therapeutic outcomes and toxicity evaluation of graphene-based nanomaterials containing rGO | |||||||||||
BSA/nano-rGO | MCF-7 cells | 100% with 0.04 µg/mL (MTT) | λ = 808 nm P = 6 W/cm2 t = 5 min | ― |
| Xenograft mice (MCF-7) 20 mg/kg |
| λ = 808 nm P = 0.6 W/cm2 t = 5 min | ― |
| [74] |
rGONM-PEG-Cy7-RGD | ― | ― | ― | ― | ― | Xenograft mice (U87MG cells) 0.2 mg/mouse |
| λ = 808 nm P = 0.1 W/cm2 t = 7 min | ― |
| [46] |
rGO- Fe2O3@Au NPs | HeLa | ≈90% with 50 µg/mL (MTT) | λ = 808 nm P = 2 W/cm2 t = 5 min | DOX n.r. AL≈100% |
| ― | ― | ― | ― | ― | [50] |
rGO nanosheets | KB | ≈95% with 20 µg/mL (CCK-8) | λ = 808 nm P = 1.2 W/cm2 t = 3 min | ― |
| Xenograft and orthotopic mice (KB cells) 5 mg/kg |
| λ = 808 nm P = 1.2 W/cm2 t = 3 min | ― |
| [69] |
131I-RGO-PEG | 4T1 | ≈90% with 200 µg/mL (CCK-8) | λ = 808 nm P = 0.5 W/cm2 t = 10 min | 131I 100 µCi |
| Xenograft and orthotopic mice (4T1cells) 10 mg/kg |
| λ = 808 nm P = 0.2 W/cm2 T = 20 min | 131I 200 µCi/ mouse |
| [51] |
rGO-AuNRVe | U87MG | 100% with 2.4 nM (CCK-8) | λ = 808 nm P = 0.25 W/cm2 t = 5 min | DOX 6.4 µg/mL AL ≈ 65% |
| Xenograft and orthotopic mice (U87MG) 10 mg/kg |
| λ = 808 nm P = 0.25 W/cm2 t = 5 min | DOX AL ≈ 65% |
| [79] |
anti-EGFR-PEG-rGO@ CPSS-Au-R6G | A549 | 100% with 100 µg/mL (MTT) | λ = 808 nm P = 0.5 W/cm2 t = 5 min | ― |
| ― | ― | ― | ― | ― | [6] |
ICG-PDA-rGO | 4T1 | ≈90% with 20 µg/mL (MTT) | λ = 808 nm P = 0.6 W/cm2 t = 5 min | ― |
| Xenograft and orthotopic mice (4T1 cells) 200 µg/mouse |
| λ = 808 nm P = 0.6 W/cm2 t = 5 min | ― |
| [59] |
rGO-GSPs | U87MG | ≈100% with 100 µg/mL (MTT) | λ = 808 nm P = 0.8 W/cm2 t = 5 min | ― |
| Xenograft mice (U87MG cells) 200 μg/mouse |
| λ = 808 nm P = 0.8 W/cm2 t = 5 min | ― |
| [66] |
rGO-mfHSA | HepG2 | ≈100% with 20 μg/mL (CCK-8) | λ = 808 nm P = 2 W/cm2 t = 5 min | ― |
| Xenograft mice (HepG2) 200 μg/mouse |
| λ = 808 nm P = 1 W/cm2 t = 10 min | ― |
| [93] |
FA-PEG-Lip@rGO/ Res | A549 MCF-7 | >90% with 80 µg/mL (w/o Res) (MTT) | λ = 780 nm P = 0.6 W/cm2 t = 10 min | Res 56 µg/mL AL ≈ 70% |
| Xenograft mice (MCF-7 cells) 2.2 mg/kg |
| λ = 780 nm P = 0.6 W/cm2 t = 5 min | Res AL ≈ 70% |
| [58] |
ArGO | ― | ― | ― | ― | ― | Xenograft mice (SCC7 cells) 5 mg/kg |
| λ = 808 nm P = 1.5 W/cm2 t = 3 min | ― |
| [77] |
AAP10-pDA/rGO | MCF-7 | ≈100% with 160 µg/mL (MTT) | λ = 808 nm P = 1.5 W/cm2 t = 5 min | AAP10 50 nM AL ≈ 0.024% |
| Xenograft mice (4T1 cells) 0.3 mg/mouse |
| λ = 808 nm P = 1.5 W/cm2 t = 5 min | AAP10 AL ≈ 0.024% |
| [90] |
Therapeutic outcomes and toxicity evaluation of graphene-based nanomaterials containing GQDs | |||||||||||
cGdots | MDA-MB231 | >70% with 500 µg/mL (MTT) | λ = 670 nm P = 0.3 W/cm2 t = 30 min | ― |
| Xenograft mice (MDA-MB231 cells) 75 µg/mouse |
| λ = 670 nm P = 0.3 W/cm2 t = 30 min irr. every other day | ― |
| [45] |
GQDs | HeLa | >90% with 1.8 µM (MTT) | λ = 670 nm P = 6.5 mW/cm2 t = 10 min | PpIX n.r. |
| Xenograft mice (MDA-MB231 cells) 80 µg/mouse |
| λ = 400–800 nm P = 80 mW/cm2 t = 10 min irr. day 1 and 7 | PpIX n.r. |
| [44] |
PLA-PEG-grafted GQDs (f-GQDs) | HeLa | ≈90% cell viability with 140 µg/mL (MTT) | ― | IP and ASODN 50 nM |
(Cytometry) | ― | ― | ― | ― | ― | [55] |
AS1411@ GQD | A549 | 100% cell viability with 5 µM (MTT) | λ = 808 nm P = 2 W/cm2 t = 10 min | AS1411n.r. |
| ― | ― | ― | ― | ― | [84] |
HA-GQD -SiO2 NPs | HeLa | 100% with 4 µM Hypo-crellin (MTT) | λ = 470 nm | Hypocre-llin 4 µM |
| ― | ― | ― | ― | ― | [94] |
GQDs@Cys-BHC | L929 HeLa MDA-MB-231 | Low toxicity with 200 µg/mL (w/o BHC) (Trypan blue, MTT) | ― | BHC ≈0.4 mM AL ≈ 88% |
| ― | ― | ― | ― | ― | [82] |
Fe3O4@SiO2 @GQDs-FA/DOX | HeLa | >90% with 50 µg/mL (MTT) | λ = 808 nm P = 0.3 W/cm2 t = 10 min | ― |
| ― | ― | ― | ― | ― | [80] |
GQD-MSN- -DOX | 4T1 | ≈95% with 100 μg/mL (CCK-8) | λ = 808 nm P = 2.5 W/cm2 t = 3 min | DOX 4.5 μg/mL AL ≈ 4.8% |
| ― | ― | ― | ― | ― | [89] |
GQD-PEG-P | A549 MCF-7 | 100% with 100 µg/mL (MTT) | λ = 980 + 636 nm P = 0.72 W/cm2 t = 10 min | ― |
| ― | ― | ― | ― | ― | [49] |
DOX@GQD- -P-Cy | 4T1 | ≈95% with 4 µg/mL (w/o DOX) (MTT) | ― | DOX 3.3 µg/mL AL ≈ 82.5% |
| Xenograft mice (4T1 cells) 1 µg /mouse |
| ― | DOX 0.8 µg /mouse AL ≈ 82.5% |
| [54] |
DL-GQD-comp | BT-474 | ≈90% with 100 µg/mL (w/o DOX) (CCK-8) | ― | DOX 8.8 µM AL ≈ 5.3% |
| ― | ― | ― | ― | ― | [63] |
IR780/GQD-FA | HeLa | ≈90% with 30 µg/mL (CCK-8) | λ = 808 nm P = 1 W/cm2 t = 5 min | ― |
| Xenograft mice (HeLa cells) 2 mg/kg |
| λ = 808 nm P = 1 W/cm2 t = 5 min | ― |
| [65] |
SCNA (DOX/GQD) | RG2 | ≈100% with 10 µg/mL (w/o DOX) (alamar blue) | λ = 808 nm P = 2 W/cm2 t = 5 min | DOX 2 µg/mL AL n.r. |
| Xenograft mice (RG2 cells) 0.2 mg/mouse |
| λ = 808 nm P = 2 W/cm2 t = 10 min | DOX 2 µg/mL AL n.r |
| [8] |
Ligands | Function | Ref. |
---|---|---|
Abs | Targets integrin (αvβ3) receptor overexpressed in cancer cells | [72] |
AGE-aptamer | Targets melanoma inhibitor of apoptosis protein (ML-IAP) overexpressed in melanoma cells | [83] |
Anti-EGFR | Targets the epidermal growth factor receptor (EGFR) of lung cancer cells | [6] |
AS1411 | Aptamer specific to malignant melanoma | [84] |
BPEI | Targets the organic anion transporting polypeptides (OATPs) overexpressed in cancer cells | [46] |
FA | Targets folic acid receptors overexpressed in cancer cells | [7,47,58,65,75,80,86] |
HA | Targets CD44 receptors, a cell surface adhesion receptor that is highly expressed in many cancers and regulates metastasis | [62] |
HER | Targets HER2+ receptors in breast cancer cells | [63] |
HSA-LA | Generates galactose residues that targets asialoglycoprotein receptor (ASGP-R), highly expressed on the surface of hepatocellular carcinoma cells (HCC) | [93] |
MMP-14(P) | Targets the overexpressed endoperoxidase in tumor cell membrane | [56] |
NGR | Targets CD13 isoform selectively overexpressed in tumor vasculature and certain tumor cells | [76] |
RGD | Targets integrin αvβ3 mAb overexpressed in cancer cells | [46] |
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Viseu, T.; Lopes, C.M.; Fernandes, E.; Real Oliveira, M.E.C.D.; Lúcio, M. A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics. Pharmaceutics 2018, 10, 282. https://doi.org/10.3390/pharmaceutics10040282
Viseu T, Lopes CM, Fernandes E, Real Oliveira MECD, Lúcio M. A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics. Pharmaceutics. 2018; 10(4):282. https://doi.org/10.3390/pharmaceutics10040282
Chicago/Turabian StyleViseu, Teresa, Carla M. Lopes, Eduarda Fernandes, Maria Elisabete C.D. Real Oliveira, and Marlene Lúcio. 2018. "A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics" Pharmaceutics 10, no. 4: 282. https://doi.org/10.3390/pharmaceutics10040282