Skip to main content
SpringerLink
Log in

Therapeutic Applications of Graphene Oxides in Angiogenesis and Cancers

  • Chapter
  • First Online:
Nanoparticles and their Biomedical Applications

Abstract

The application of nanotechnology in biology and medicine is generally termed as nanomedicine which reforms the strategic platforms of the modern healthcare system associated with diagnosis and therapy of different diseases. Since past decades, several research groups including ours demonstrated the diverse biomedical applications of different inorganic nanoparticles. Among these nanomaterials, graphene oxide (GO) nanoparticles are of great attraction for their potent applications in angiogenesis as well as cancer therapy due to its unique physicochemical and biological properties such as large surface area, high drug loading efficacy, biocompatibility, biodegradability, etc. This book chapter illustrates the overview of recent applications of GO in angiogenesis including pro-angiogenic activity, anti-angiogenic activity and wound healing potential. Moreover, the therapeutic (anticancer activity, drug/gene delivery, photothermal/immuno therapy) and bio-imaging applications of GO for different cancer diseases are also described in a concise manner. Additionally, in view of future clinical applications, pharmacokinetics, toxicity and clearance studies of GO are briefly demonstrated. Finally, this book chapter provides the global market overview along with challenges and future directions of GO in biomedical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

A549:

Human alveolar adenocarcinoma epithelial cell line

Ab:

Antibody

ADM:

Acellular dermal matrix

AIE:

Aggregation-induced emission

APCs:

Antigen-presenting cells

B16:

Murine melanoma cells

Bcl-2:

B-cell lymphoma-2

bFGF:

Basic fibroblast growth factor

BSA:

Bovine serum albumin

CAD:

Cis-aconitic anhydride-modified doxorubicin

CAM:

Chick chorioallantoic membrane

CEA:

Chick embryo angiogenesis

CMC:

Carboxymethylcellulose

CpG:

Cytosine-phosphate-guanine

CS-PVA:

Chitosan-polyvinyl alcohol

CT:

Computed tomography

Cx43:

Connexin43

DCs:

Dendritic cells

DDS:

Drug delivery system

DIM:

Diindolylmethane

DNA:

Deoxyribonucleic acid

DOX:

Doxorubicin

E. coli :

Escherichia coli

ECM:

Extracellular matrix

EGFP:

Enhanced green fluorescence protein

eNOS:

Endothelial nitric oxide synthase

EPR:

Enhanced permeability and retention

FA:

Folic acid

FDA:

Food and drug administration

fGO:

Functionalized graphene oxide

FITC:

Fluorescein isothiocyanate

FSHR:

Follicle-stimulating hormone receptor

GelMA:

Methacrylated gelatin

GF:

Graphene foams

GIC:

Graphene intercalation compounds

GO:

Graphene oxide

GPD:

GO-PEG-PAMAM

H2SO4:

Sulphuric acid

HBD:

Heparin-binding domain

HDAC:

Histone deacetylases

HeLa:

Human cervical cancer cells

HGF:

Hepatocyte growth factor

HNO3:

Nitric acid

HUVECs:

Human umbilical vein endothelial cells

IDO:

Immune checkpoint overexpressed in tumours

IL1β:

Interleukin-1 beta

IL6:

Interleukin 6

IR800:

Infrared 800

IUPAC:

International union of pure and applied chemistry

KClO3:

Potassium chlorate

LDI:

Laser Doppler imaging

LHT7:

Low molecular weight heparin

LSECs:

Liver sinusoidal endothelial cells

MBA-MB-231:

Human breast cancer cell line

MCF-7:

Human breast cancer cell line

MCP-1:

Monocyte chemotactic protein 1

MDR:

Multidrug-resistant

MIA PaCA-2:

Human pancreatic carcinoma

MMP-9:

Matrix metallopeptidase 9

MRI:

Magnetic resonance imaging

MSCs:

Mesenchymal stem cells

NIR:

Near-infrared

NO:

Nitric oxide

OVA:

Ovalbumin

PAACA:

Poly(acryloyl-6-aminocaproic acid)

PAH:

Polyallylamine hydrochloride

PAMAM:

Polyamidoamine dendrimer

PDDA:

Poly(diallyldimethylammonium chloride)

PDGF:

Platelet-derived growth factor

pDNA:

Plasmid DNA

PEG:

Polyethylene glycol

PEI:

Polyethyleneimine

PET:

Positron emission tomography

PGO:

Porphyrin graphene oxide

PI:

Propidium iodide

PMAA:

Poly(methacrylic acid)

PPa:

Pyropheophorbide-a

PTX:

Paclitaxel

PVP:

Poly N-vinylpyrrolidone

RAW 264.7:

Murine macrophage cell line

RES:

Reticuloendothelial system

rGO:

Reduced graphene oxide

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

S. aureus :

Staphylococcus aureus

SCC-7:

Mouse head and neck carcinoma cell line

shRNA:

Short hairpin RNA

SiHa:

Cervical squamous cancer cells

siRNA:

Short interfering RNA

SPION:

Superparamagnetic iron oxide nanoparticles

SRGO:

Sorafenib reduced graphene oxide

TiO2:

Titanium dioxide

TLR:

Toll-like receptor

TNFα:

Tumour necrosis factor alpha

U118:

Human brain glioma cells

U87:

Human primary glioblastoma cell line

UCNPs:

Upconversion nanoparticles

Ure B:

Urease B

VAR:

Peptide probe

VEGF:

Vascular endothelial growth factor

ZnO:

Zinc oxide

ZnPc:

Zn(II)-phthalocyanine

References

  • Afarideh B, Rajabibazl M, Omidi M et al (2018) Anticancer activity of graphene oxide/5-FU on CT26 Ds-Red adenocarcinoma cell line. Orient J Chem 34:2002

    Article  CAS  Google Scholar 

  • Ahmad MW, Xu W, Kim SJ et al (2015) Potential dual imaging nanoparticle: Gd2O3 nanoparticle. Sci Rep 5:8549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhavan O, Ghaderi E, Aghayee S et al (2012) The use of a glucose-reduced graphene oxide suspension for photothermal cancer therapy. J Mater Chem 22:13773–13781

    Article  CAS  Google Scholar 

  • Arvizo RR, Rana S, Miranda OR et al (2011) Mechanism of anti-angiogenic property of gold nanoparticles: role of nanoparticle size and surface charge. Nanomedicine 7:580–587

    Article  CAS  PubMed  Google Scholar 

  • Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153:198–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bansal A, Zhang Y (2014) Photocontrolled nanoparticle delivery systems for biomedical applications. Acc Chem Res 47:3052–3060

    Article  CAS  PubMed  Google Scholar 

  • Bartczak D, Muskens OL, Sanchez-Elsner T et al (2013) Manipulation of in vitro angiogenesis using peptide-coated gold nanoparticles. ACS Nano 7:5628–5636

    Article  CAS  PubMed  Google Scholar 

  • Barui AK, Veeriah V, Mukherjee S et al (2012) Zinc oxide nanoflowers make new blood vessels. Nanoscale 4:7861–7869

    Article  CAS  PubMed  Google Scholar 

  • Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8:592–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bikfalvi A, Bicknell R (2002) Recent advances in angiogenesis, anti-angiogenesis and vascular targeting. Trends Pharmacol Sci 23:576–582

    Article  CAS  PubMed  Google Scholar 

  • Boehm H-P, Setton R, Stumpp E (1994) Nomenclature and terminology of graphite intercalation compounds. Pure Appl Chem 66:1893–1901

    Article  CAS  Google Scholar 

  • Borghaei H, Smith MR, Campbell KS (2009) Immunotherapy of cancer. Eur J Pharmacol 625:41–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brodie BC (1859) On the atomic weight of graphite. Philos Trans R Soc London 149:249–259

    Google Scholar 

  • Byun J (2015) Emerging frontiers of graphene in biomedicine. J Microbiol Biotechnol 25:145–151

    Article  CAS  PubMed  Google Scholar 

  • Caruso F, Hyeon T, Rotello VM (2012) Nanomedicine. Chem Soc Rev 41:2537–2538

    Article  CAS  PubMed  Google Scholar 

  • Chang Y, Yang ST, Liu JH et al (2011) In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol Lett 200:201–210

    Article  CAS  PubMed  Google Scholar 

  • Chaudhuri P, Harfouche R, Soni S et al (2010) Shape effect of carbon nanovectors on angiogenesis. ACS Nano 4:574–582

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Chen HR, Shi JL (2014) Inorganic nanoparticle-based drug codelivery nanosystems to overcome the multidrug resistance of cancer cells. Mol Pharm 11:2495–2510

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Liu L, Jiang C (2016) Charge-reversal nanoparticles: novel targeted drug delivery carriers. Acta Pharm Sin B 6:261–267

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheon YA, Bae JH, Chung BG (2016) Reduced graphene oxide nanosheet for chemo-photothermal therapy. Langmuir 32:2731–2736

    Article  CAS  PubMed  Google Scholar 

  • Chidambaram M, Manavalan R, Kathiresan K (2011) Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J Pharm Pharm Sci 14:67–77

    Article  PubMed  Google Scholar 

  • Cho K, Wang X, Nie S et al (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316

    Article  CAS  PubMed  Google Scholar 

  • Cho WS, Kang BC, Lee JK et al (2013) Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration. Part Fibre Toxicol 10:9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu J, Shi P, Yan W et al (2018) PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing. Nanoscale 10:9547–9560

    Article  CAS  PubMed  Google Scholar 

  • Cong HP, Wang P, Yu SH (2013) Stretchable and self-healing graphene oxide-polymer composite hydrogels: a dual-network design. Chem Mater 25:3357–3362

    Article  CAS  Google Scholar 

  • Cotton FA, Wilkinsion G (1972) Advanced inorganc chemistry, 3rd edn. Wiley, Chichester, ISBN: 0-471-17560-9

    Google Scholar 

  • Dai L (2006) Carbon nanotechnology recent developments in chemistry, physics, materials science and device applications. Elsevier, Amsterdam, ISBN-10: 044451855X

    Google Scholar 

  • Danhier F, Feron O, Preat V (2010) To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148:135–146

    Article  CAS  PubMed  Google Scholar 

  • Das S, Singh S, Dowding JM et al (2012) The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 33:7746–7755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deb A, Andrews NG, Raghavan V (2018) Natural polymer functionalized graphene oxide for co-delivery of anticancer drugs: in-vitro and in-vivo. Int J Biol Macromol 113:515–525

    Article  CAS  PubMed  Google Scholar 

  • Di Santo R, Digiacomo L, Palchetti S et al (2019) Microfluidic manufacturing of surface-functionalized graphene oxide nanoflakes for gene delivery. Nanoscale 11:2733–2741

    Article  PubMed  Google Scholar 

  • Draz MS, Fang BA, Zhang P et al (2014) Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and viral infections. Theranostics 4:872–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dreyer DR, Ruoff RS, Bielawski CW (2010) From conception to realization: an historial account of graphene and some perspectives for its future. Angew Chem 49:9336–9344

    Article  CAS  Google Scholar 

  • Enterkin JA, Poeppelmeier KR, Marks LD (2011) Oriented catalytic platinum nanoparticles on high surface area strontium titanate nanocuboids. Nano Lett 11:993–997

    Article  CAS  PubMed  Google Scholar 

  • Erathodiyil N, Ying JY (2011) Functionalization of inorganic nanoparticles for bioimaging applications. Acc Chem Res 44:925–935

    Article  CAS  PubMed  Google Scholar 

  • Falkowski P, Scholes RJ, Boyle EE et al (2000) The global carbon cycle: a test of our knowledge of earth as a system. Science 290:291–296

    Article  CAS  PubMed  Google Scholar 

  • Fan ZJ, Liu B, Wang J et al (2014) A novel wound dressing based on Ag/Graphene polymer hydrogel: effectively kill bacteria and accelerate wound healing. Adv Funct Mater 24:3933–3943

    Article  CAS  Google Scholar 

  • Feng L, Liu Z (2011) Graphene in biomedicine: opportunities and challenges. Nanomedicine (Lond) 6:317–324

    Article  CAS  Google Scholar 

  • Feng L, Zhang S, Liu Z (2011) Graphene based gene transfection. Nanoscale 3:1252–1257

    Article  CAS  PubMed  Google Scholar 

  • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  CAS  PubMed  Google Scholar 

  • Geim AK, Novoselov KS (2007) The rise of graphene. Nat Mater 6:183–191

    Article  CAS  PubMed  Google Scholar 

  • Gu Y, Guo Y, Wang C et al (2017) A polyamidoamne dendrimer functionalized graphene oxide for DOX and MMP-9 shRNA plasmid co-delivery. Mater Sci Eng C Mater Biol Appl 70:572–585

    Article  CAS  PubMed  Google Scholar 

  • Gulzar A, Xu J, Yang D et al (2018) Nano-graphene oxide-UCNP-Ce6 covalently constructed nanocomposites for NIR-mediated bioimaging and PTT/PDT combinatorial therapy. Dalton Trans (Cambridge, England) 2003(47):3931–3939

    Article  Google Scholar 

  • Gurunathan S, Lee KJ, Kalishwaralal K et al (2009) Antiangiogenic properties of silver nanoparticles. Biomaterials 30:6341–6350

    Article  CAS  PubMed  Google Scholar 

  • Gurunathan S, Han JW, Eppakayala V et al (2013) Green synthesis of graphene and its cytotoxic effects in human breast cancer cells. Int J Nanomedicine 8:1015–1027

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hamidi M, Azadi A, Rafiei P et al (2013) A pharmacokinetic overview of nanotechnology-based drug delivery systems: an ADME-oriented approach. Crit Rev Ther Drug Carrier Syst 30:435–467

    Article  CAS  PubMed  Google Scholar 

  • Hijaz M et al (2016) Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer. BMC Cancer 16:220

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Holgate ST (2010) Exposure, uptake, distribution and toxicity of nanomaterials in humans. J Biomed Nanotechnol 6:1–19

    Article  CAS  PubMed  Google Scholar 

  • Hong H, Zhang Y, Engle JW et al (2012) In vivo targeting and positron emission tomography imaging of tumor vasculature with Ga-66-labeled nano-graphene. Biomaterials 33:4147–4156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu H, You YY, He LZ et al (2015) The rational design of NAMI-A-loaded mesoporous silica nanoparticles as antiangiogenic nanosystems. J Mater Chem B 3:6338–6346

    Article  CAS  PubMed  Google Scholar 

  • Huang C, Wu J, Jiang W et al (2018) Amphiphilic prodrug-decorated graphene oxide as a multi-functional drug delivery system for efficient cancer therapy. Mater Sci Eng C Mater Biol Appl 89:15–24

    Article  CAS  PubMed  Google Scholar 

  • Jaleel JA, Sruthi S, Pramod K (2017) Reinforcing nanomedicine using graphene family nanomaterials. J Control Release 255:218–230

    Article  CAS  PubMed  Google Scholar 

  • Jasim DA, Menard-Moyon C, Begin D et al (2015) Tissue distribution and urinary excretion of intravenously administered chemically functionalized graphene oxide sheets. Chem Sci 6:3952–3964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaworski S, Sawosz E, Kutwin M et al (2015) In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma. Int J Nanomedicine 10:1585–1596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jong WHD, Borm PJ (2008) Drug delivery and nanoparticles:applications and hazards. Int J Nanomedicine 3:133–149

    Article  PubMed  PubMed Central  Google Scholar 

  • Josefsen LB, Boyle RW (2012) Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics. Theranostics 2:916–966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang K, Lim DH, Choi IH et al (2011) Vascular tube formation and angiogenesis induced by polyvinylpyrrolidone-coated silver nanoparticles. Toxicol Lett 205:227–234

    Article  CAS  PubMed  Google Scholar 

  • Kang S, Kim KM, Son Y et al (2019) Graphene oxide quantum dots derived from coal for bioimaging: facile and green approach. Sci Rep 9:4101

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Khot LR, Sankaran S, Maja JM et al (2012) Applications of nanomaterials in agricultural production and crop protection: a review. Crop Prot 35:64–70

    Article  CAS  Google Scholar 

  • Kiew SF, Kiew LV, Lee HB et al (2016) Assessing biocompatibility of graphene oxide-based nanocarriers: a review. J Control Release 226:217–228

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, Shim G, Choi HW et al (2012) Tumor vasculature targeting following co-delivery of heparin-taurocholate conjugate and suberoylanilide hydroxamic acid using cationic nanolipoplex. Biomaterials 33:4424–4430

    Article  CAS  PubMed  Google Scholar 

  • Krishnamachari Y, Geary SM, Lemke CD et al (2011) Nanoparticle delivery systems in cancer vaccines. Pharm Res 28:215–236

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Chatterjee K (2016) Comprehensive review on the use of graphene-based substrates for regenerative medicine and biomedical devices. ACS Appl Mater Interfaces 8:26431–26457

    Article  CAS  PubMed  Google Scholar 

  • Lai PX, Chen CW, Wei SC et al (2016) Ultrastrong trapping of VEGF by graphene oxide: anti-angiogenesis application. Biomaterials 109:12–22

    Article  CAS  PubMed  Google Scholar 

  • Leteba GM, Lang CI (2013) Synthesis of bimetallic platinum nanoparticles for biosensors. Sensors (Basel) 13:10358–10369

    Article  CAS  Google Scholar 

  • Li SD, Huang L (2008) Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm 5:496–504

    Article  CAS  PubMed  Google Scholar 

  • Li SH, Aphale AN, Macwan IG et al (2012) Graphene oxide as a quencher for fluorescent assay of amino acids, peptides, and proteins. ACS Appl Mater Interfaces 4:7068–7074

    Google Scholar 

  • Li B, Yang J, Huang Q et al (2013) Biodistribution and pulmonary toxicity of intratracheally instilled graphene oxide in mice. NPG Asia Materials 5:e44

    Article  CAS  Google Scholar 

  • Li Y, Dong H, Li Y et al (2015a) Graphene-based nanovehicles for photodynamic medical therapy. Int J Nanomedicine 10:2451–2459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Wang H, Yang B et al (2015b) Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring. Mater Sci Eng C Mater Biol Appl 57:181–188

    Article  CAS  PubMed  Google Scholar 

  • Li QR, Jiao JB, Li LL et al (2017) Graphene oxide-enhanced cytoskeleton imaging and mitosis tracking. Chem Commun (Camb) 53:3373–3376

    Article  CAS  Google Scholar 

  • Liao KH, Lin YS, Macosko CW et al (2011) Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Appl Mater Interfaces 3:2607–2615

    Article  CAS  PubMed  Google Scholar 

  • Lin S, Ruan J, Wang S (2019) Biosynthesized of reduced graphene oxide nanosheets and its loading with paclitaxel for their anti cancer effect for treatment of lung cancer. J Photochem Photobiol B 191:13–17

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Yu D, Zeng C et al (2010) Biocompatible graphene oxide-based glucose biosensors. Langmuir 26:6158–6160

    Article  CAS  PubMed  Google Scholar 

  • Liu JH, Yang ST, Wang HF et al (2012) Effect of size and dose on the biodistribution of graphene oxide in mice. Nanomedicine 7:1801–1812

    Article  CAS  PubMed  Google Scholar 

  • Liu P, Wang S, Liu X et al (2018) Platinated graphene oxide: a nanoplatform for efficient gene-chemo combination cancer therapy. Eur J Pharm Sci 21:319–329

    Article  CAS  Google Scholar 

  • Lohse SE, Murphy CJ (2012) Applications of colloidal inorganic nanoparticles: from medicine to energy. J Am Chem Soc 134:15607–15620

    Article  CAS  PubMed  Google Scholar 

  • Lu CH, Zhu CL, Li J et al (2010) Using graphene to protect DNA from cleavage during cellular delivery. Chem Commun 46:3116–3118

    Article  CAS  Google Scholar 

  • Lu B, Li T, Zhao H et al (2012) Graphene-based composite materials beneficial to wound healing. Nanoscale 4:2978–2982

    Article  CAS  PubMed  Google Scholar 

  • Lu C, Huang PJ, Liu B et al (2016) Comparison of graphene oxide and reduced graphene oxide for dna adsorption and sensing. Langmuir 32:10776–10783

    Article  CAS  PubMed  Google Scholar 

  • Luo L, Xu L, Zhao H (2017) Biosynthesis of reduced graphene oxide and its in-vitro cytotoxicity against cervical cancer (HeLa) cell lines. Mater Sci Eng C Mater Biol Appl 78:198–202

    Article  CAS  PubMed  Google Scholar 

  • Luo Y, Tang Y, Liu T et al (2019) Engineering graphene oxide with ultrasmall SPIONs and smart drug release for cancer theranostics. Chem Commun 55:1963–1966

    Article  Google Scholar 

  • Ma H, Liu J, Ali MM et al (2015) Nucleic acid aptamers in cancer research, diagnosis and therapy. Chem Soc Rev 44:1240–1256

    Article  CAS  PubMed  Google Scholar 

  • Mallick A, Nandi A, Basu S (2019) Polyethylenimine coated graphene oxide nanoparticles for targeting mitochondria in cancer cells. ACS Appl Bio Mater 2:14–19

    Article  CAS  PubMed  Google Scholar 

  • Marketsandmarkets.com Report (2017) Graphene market worth 278.47 Million USD by 2020. http://www.marketsandmarketscom/PressReleases/grapheneasp

  • Mattos AJP, Raquel FE, Anna DR (2014) Gold nanoparticle mediated cancer immunotherapy. Nanomedicine 10:503–514

    Article  CAS  Google Scholar 

  • McNaught AD, Wilkinson A (1997) IUPAC. Compendium of chemical terminology, 2nd edn. Blackwell Scientific Publications, Oxford

    Google Scholar 

  • Meghana S, Kabra P, Chakraborty S et al (2015) Understanding the pathway of antibacterial activity of copper oxide nanoparticles. RSC Adv 5:12293–12299

    Article  CAS  Google Scholar 

  • Millstone JE, Kavulak DF, Woo CH et al (2010) Synthesis, properties, and electronic applications of size-controlled poly(3-hexylthiophene) nanoparticles. Langmuir 26:13056–13061

    Article  CAS  PubMed  Google Scholar 

  • Mittal S, Kumar V, Dhiman N et al (2016) Physico-chemical properties based differential toxicity of graphene oxide/reduced graphene oxide in human lung cells mediated through oxidative stress. Sci Rep 6:15860

    Google Scholar 

  • Muazim K, Hussain Z (2017) Graphene oxide - a platform towards theranostics. Mater Sci Eng C Mater Biol Appl 76:1274–1288

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee S, Sushma V, Patra S et al (2012) Green chemistry approach for the synthesis and stabilization of biocompatible gold nanoparticles and their potential applications in cancer therapy. Nanotechnology 23:455103

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S, Sriram P, Barui AK et al (2015) Graphene oxides show angiogenic properties. Adv Healthc Mater 4:1722–1732

    Article  CAS  PubMed  Google Scholar 

  • Mulcahy N (2008) Cancer to become leading cause of death worldwide. Medscape

    Google Scholar 

  • Nanda SS, Yi DK, Kim K (2016) Study of antibacterial mechanism of graphene oxide using Raman spectroscopy. Sci Rep 6:28443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nejabat M, Charbgoo F, Ramezani M (2017) Graphene as multifunctional delivery platform in cancer therapy. J Biomed Mater Res A 105:2355–2367

    Article  CAS  PubMed  Google Scholar 

  • Nguyen DT, Orgill DP, Murphy GF (2009) The pathophysiologic basis for wound healing and cutaneous regeneration, Biomaterials for treating skin loss. Woodhead Publishing, Boca Raton, pp 25–57

    Google Scholar 

  • Nicol W (2015) A material supreme: how graphene will shape the world of tomorrow digital trends

    Google Scholar 

  • Nie W, Peng C, Zhou X et al (2017) Three-dimensional porous scaffold by self-assembly of reduced graphene oxide and nano-hydroxyapatite composites for bone tissue engineering. Carbon 116:325–337

    Article  CAS  Google Scholar 

  • Nolan CP, DeAngelis LM (2015) Neurologic complications of chemotherapy and radiation therapy. Continuum (Minneap Minn) 21:429–451

    Google Scholar 

  • Novoselov KS, Geim AK, Morozov SV et al (2004) Electric field effect in atomically thin carbon films. Science 306:666–669

    Article  CAS  PubMed  Google Scholar 

  • Nurunnabi M, Parvez K, Nafiujjaman M et al (2015) Bioapplication of graphene oxide derivatives: drug/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges. RSC Adv 5:42141–42161

    Article  CAS  Google Scholar 

  • Orecchioni M, Cabizza R, Bianco A et al (2015) Graphene as cancer theranostic tool: progress and future challenges. Theranostics 5:710–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orecchioni M, Jasim DA, Pescatori M et al (2016a) Molecular and genomic impact of large and small lateral dimension graphene oxide sheets on human immune cells from healthy donors. Adv Healthc Mater 5:276–287

    Article  CAS  PubMed  Google Scholar 

  • Orecchioni M, Menard-Moyon C, Delogu LG et al (2016b) Graphene and the immune system: challenges and potentiality. Adv Drug Deliv Rev 105:163–175

    Article  CAS  PubMed  Google Scholar 

  • Ou LL, Song B, Liang H et al (2016) Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms. Part Fibre Toxicol 13:57

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ouay LB, Stellacci F (2015) Antibacterial activity of silver nanoparticles: a surface science insight. Nano Today 10:339–354

    Article  CAS  Google Scholar 

  • Park J, Kim YS, Ryu S et al (2015) Graphene potentiates the myocardial repair efficacy of mesenchymal stem cells by stimulating the expression of angiogenic growth factors and gap junction protein. Adv Func Mater 25:2590–2600

    Article  CAS  Google Scholar 

  • Patra CR (2015) Graphene oxides and the angiogenic process. Nanomedicine (Lond) 10:2959–2962

    Article  CAS  Google Scholar 

  • Patra CR, Bhattacharya R, Patra S et al (2008) Pro-angiogenic properties of europium(III) hydroxide nanorods. Adv Mater 20:753–756

    Article  CAS  Google Scholar 

  • Patra CR, Kim JH, Pramanik K et al (2011) Reactive oxygen species driven angiogenesis by inorganic nanorods. Nano Lett 11:4932–4938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul A, Hasan A, Kindi HA et al (2014) Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair. ACS Nano 8:8050–8062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perreault F, de Faria AF, Nejati S et al (2015) Antimicrobial properties of graphene oxide nanosheets: why size matters. ACS Nano 9:7226–7236

    Article  CAS  PubMed  Google Scholar 

  • Rahman M, Akhter S, Ahmad MZ et al (2015) Emerging advances in cancer nanotheranostics with graphene nanocomposites: opportunities and challenges. Nanomedicine 10:2405–2422

    Article  CAS  PubMed  Google Scholar 

  • Raj S, Jose S, Sumod US et al (2012) Nanotechnology in cosmetics: opportunities and challenges. J Pharm Bioallied Sci 4:186–193

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ren L, Zhang Y, Cui C et al (2017) Functionalized graphene oxide for anti-VEGF siRNA delivery: preparation, characterization and evaluation in vitro and in vivo. RSC Adv 7:20553–20566

    Article  CAS  Google Scholar 

  • Report B (2014) Autumn statement 2014: Manchester to get £235m science research centre. http://www.bbccom/news/uk-england-30309451

  • Report D (2016) Graphene: research now, reap next decade. https://www2.deloitte.com/global/en/pages/technology-media-and-telecommunications/articles/tmt-pred16-tech-graphene-research-now-reap-next-decade.html

  • Report Gc (2017) Graphene market Size and trend analysis by product (Nanoplatelets, Oxide), by application (Electronics, Composites, Energy), by region (North America, Europe, Asia Pacific, Rest of the World), and Segment forecasts, 2014–2025. http://www.grandviewresearchcom/industry-analysis/graphene-industry

  • Rieger S, Zhao H, Martin P et al (2015) The role of nuclear hormone receptors in cutaneous wound repair. Cell Biochem Funct 33:1–13

    Article  CAS  PubMed  Google Scholar 

  • Robinson JT, Tabakman SM, Liang YY et al (2011) Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. J Am Chem Soc 133:6825–6831

    Article  CAS  PubMed  Google Scholar 

  • Sahne F, Mohammadi M, Najafpour GD (2019) Single-layer assembly of multifunctional carboxymethylcellulose on graphene oxide nanoparticles for improving in vivo curcumin delivery into tumor cells. ACS Biomater Sci Eng 5(5):2595–2609

    Article  CAS  PubMed  Google Scholar 

  • Sahu SC, Casciano DA (eds) (2009) Nanotoxicity: from in vivo and in vitro models to health risks. Wiley, Chichester

    Google Scholar 

  • Schaefer H-E (2010) Nanoscience. The science of the small in physics, engineering, chemistry, biology and medicine. Springer, New York

    Google Scholar 

  • Schafhaeutl C (1840) LXXXVI. On the combinations of carbon with silicon and iron, and other metals, forming the different species of cast iron, steel, and malleable iron. London, Edinburgh, Dublin Philos Mag J Sci 16:570–590

    Article  Google Scholar 

  • Shi S, Yang K, Hong H et al (2013) Tumor vasculature targeting and PET imaging in living mice with reduced graphene oxide. Eur J Nucl Med Mol Imaging 40:S153–S153

    Google Scholar 

  • Shim G, Kim JY, Han J et al (2014) Reduced graphene oxide nanosheets coated with an anti-angiogenic anticancer low-molecular-weight heparin derivative for delivery of anticancer drugs. J Control Release 189:80–89

    Article  CAS  PubMed  Google Scholar 

  • Shin SR, Li YC, Jang HL et al (2016a) Graphene-based materials for tissue engineering. Adv Drug Deliv Rev 105:255–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin SR, Zihlmann C, Akbari M et al (2016b) Reduced graphene oxide-GelMA hybrid hydrogels as scaffolds for cardiac tissue engineering. Small 12:3677–3689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steichen SD, Caldorera-Moore M, Peppas NA (2013) A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur J Pharm Sci 48:416–427

    Article  CAS  PubMed  Google Scholar 

  • Su SH, Wang JL, Wei JH et al (2015) Efficient photothermal therapy of brain cancer through porphyrin functionalized graphene oxide. New J Chem 39:5743–5749

    Article  CAS  Google Scholar 

  • Sun X, Liu Z, Welsher K et al (2008) Nano-graphene oxide for cellular imaging and drug delivery. Nano Res 1:203–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun ZC, Huang P, Tong G et al (2013) VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle. Nanoscale 5:6857–6866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun X, Zebibula A, Dong X et al (2018) Aggregation-induced emission nanoparticles encapsulated with PEGylated nano graphene oxide and their applications in two-photon fluorescence bioimaging and photodynamic therapy in vitro and in vivo. ACS Appl Mater Interfaces 10:25037–25046

    Article  CAS  PubMed  Google Scholar 

  • Syama S, Paul W, Sabareeswaran A et al (2017) Raman spectroscopy for the detection of organ distribution and clearance of PEGylated reduced graphene oxide and biological consequences. Biomaterials 131:121–130

    Article  CAS  PubMed  Google Scholar 

  • Tan YB, Lee JM (2013) Graphene for supercapacitor applications. J Mater Chem A 1:14814–14843

    Article  CAS  Google Scholar 

  • Tang P, Han L, Li P et al (2019) Mussel-inspired electroactive and antioxidative scaffolds with incorporation of polydopamine-reduced graphene oxide for enhancing skin wound healing. ACS Appl Mater Interfaces 11:7703–7714

    Article  CAS  PubMed  Google Scholar 

  • Tao Y, Ju EG, Ren JS, Qu XG (2014) Immunostimulatory oligonucleotides-loaded cationic graphene oxide with photothermally enhanced immunogenicity for photothermal/immune cancer therapy. Biomaterials 35:9963–9971

    Article  CAS  PubMed  Google Scholar 

  • Teli MK, Mutalik S, Rajanikant GK (2010) Nanotechnology and nanomedicine: going small means aiming big. Curr Pharm Des 16:1882–1892

    Article  CAS  PubMed  Google Scholar 

  • Thangavel P, Kannan R, Ramachandran B et al (2018) Development of reduced graphene oxide (rGO)-isabgol nanocomposite dressings for enhanced vascularization and accelerated wound healing in normal and diabetic rats. J Colloid Interface Sci 517:251–264

    Article  CAS  PubMed  Google Scholar 

  • Tian J, Luo Y, Huang L et al (2016) Pegylated folate and peptide-decorated graphene oxide nanovehicle for in vivo targeted delivery of anticancer drugs and therapeutic self-monitoring. Biosens Bioelectron 80:519–524

    Article  CAS  PubMed  Google Scholar 

  • Torchilin VP (2010) Passive and active drug targeting: drug delivery to tumors as an example. Handb Exp Pharmacol 197:50

    Google Scholar 

  • Tran TH, Nguyen HT, Pham TT et al (2015) Development of a graphene oxide nanocarrier for dual-drug chemo-phototherapy to overcome drug resistance in cancer. ACS Appl Mater Interfaces 7:28647–28655

    Article  CAS  PubMed  Google Scholar 

  • Velnar T, Bailey T, Smrkolj V (2009) The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 37:1528–1542

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Hu R, Lin G et al (2013) Functionalized quantum dots for biosensing and bioimaging and concerns on toxicity. ACS Appl Mater Interfaces 5:2786–2799

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Zhou F, Zhang D et al (2016) A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy. Nanoscale 8:3530–3538

    Article  CAS  PubMed  Google Scholar 

  • Wierzbicki M, Sawosz E, Grodzik M et al (2013) Comparison of anti-angiogenic properties of pristine carbon nanoparticles. Nanoscale Res Lett 8:195

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Winter JO (2007) Nanoparticles and nanowires for cellular engineering. Nanotechnologies for the life sciences. Wiley, New York

    Google Scholar 

  • Wu CH, He QM, Zhu AN et al (2014) Synergistic anticancer activity of photo- and chemoresponsive nanoformulation based on polylysine-functionalized graphene. ACS Appl Mater Interfaces 6:21615–21623

    Article  CAS  PubMed  Google Scholar 

  • Wu SY, An SS, Hulme J (2015) Current applications of graphene oxide in nanomedicine. Int J Nanomedicine 10(Spec Iss):9–24

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xing FY, Guan LL, Li YL et al (2016) Biosynthesis of reduced graphene oxide nanosheets and their in vitro cytotoxicity against cardiac cell lines of Catla catla. Environ Toxicol Pharmacol 48:110–115

    Article  CAS  PubMed  Google Scholar 

  • Xu LG, Xiang J, Liu Y et al (2016) Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity. Nanoscale 8:3785–3795

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Tang X, Wu X et al (2019) Biosynthesis of sorafenib coated graphene nanosheets for the treatment of gastric cancer in patients in nursing care. J Photochem Photobiol B 191:1–5

    Article  CAS  PubMed  Google Scholar 

  • Yaacoub K, Pedeux R, Tarte K et al (2016) Role of the tumor microenvironment in regulating apoptosis and cancer progression. Cancer Lett 378:150–159

    Article  CAS  PubMed  Google Scholar 

  • Yadav N, Kumar N, Prasad P et al (2018) Stable dispersions of covalently tethered polymer improved graphene oxide nanoconjugates as an effective vector for siRNA delivery. ACS Appl Mater Interfaces 10:14577–14593

    Article  CAS  PubMed  Google Scholar 

  • Yan M, Liu Y, Zhu X et al (2019) Nanoscale reduced graphene oxide-mediated photothermal therapy together with IDO inhibition and PD-L1 blockade synergistically promote antitumor immunity. ACS Appl Mater Interfaces 11:1876–1885

    Article  CAS  PubMed  Google Scholar 

  • Yang XY, Zhang XY, Liu ZF et al (2008) High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J Phys Chem C 112:17554–17558

    Article  CAS  Google Scholar 

  • Yang K, Wan JM, Zhang SA et al (2011) In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. ACS Nano 5:516–522

    Article  CAS  PubMed  Google Scholar 

  • Yang K, Wan JM, Zhang S et al (2012) The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. Biomaterials 33:2206–2214

    Article  CAS  PubMed  Google Scholar 

  • Yang K, Gong H, Shi XZ et al (2013) In vivo biodistribution and toxicology of functionalized nano-graphene oxide in mice after oral and intraperitoneal administration. Biomaterials 34:2787–2795

    Article  CAS  PubMed  Google Scholar 

  • Yang DZ, Feng L, Dougherty CA et al (2016) In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide. Biomaterials 104:361–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin F, Hu K, Chen Y et al (2017) SiRNA delivery with PEGylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer. Theranostics 7:1133–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshioka Y, Higashisaka K, Tsunoda S, Tsutsumi Y (2014) The absorption, distribution, metabolism, and excretion profile of nanoparticles. In: Akashi M, Akagi T, Matsusaki M (eds) Engineered cell manipulation for biomedical application. Nanomedicine and nanotoxicology. Springer, Tokyo, pp 259–271

    Chapter  Google Scholar 

  • You DG, Deepagan VG, Um W et al (2016) ROS-generating TiO2 nanoparticles for non-invasive sonodynamic therapy of cancer. Sci Rep 6:23200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yue H, Wei W, Gu Z et al (2015) Exploration of graphene oxide as an intelligent platform for cancer vaccines. Nanoscale 7:19949–19957

    Article  CAS  PubMed  Google Scholar 

  • Yue H, Zhou X, Cheng M et al (2018) Graphene oxide-mediated Cas9/sgRNA delivery for efficient genome editing. Nanoscale 10:1063–1071

    Article  CAS  PubMed  Google Scholar 

  • Zang Z, Zeng X, Wang M et al (2017) Tunable photoluminescence of water-soluble AgInZnS-graphene oxide (GO) nanocompositesand their application in-vivo bioimaging. Sens Actuators B Chem 252:1179–1186

    Article  CAS  Google Scholar 

  • Zare-Zardini H, Taheri-Kafrani A, Amiri A et al (2018) New generation of drug delivery systems based on ginsenoside Rh2-, Lysine- and Arginine-treated highly porous graphene for improving anticancer activity. Sci Rep 8:586

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhang LM, Lu ZX, Zhao QH et al (2011) Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide. Small 7:460–464

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Kim JA, Huang AYC (2018) Optimizing tumor microenvironment for cancer immunotherapy: β-Glucan-based nanoparticles. Front Immunol 9:341–341

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Zhao X, Yang L, Li X et al (2015) Functionalized graphene oxide nanoparticles for cancer cell-specific delivery of antitumor drug. Bioconjug Chem 26:128–136

    Article  CAS  PubMed  Google Scholar 

  • Zhao H, Osborne OJ, Lin S et al (2016) Lanthanide hydroxide nanoparticles induce angiogenesis via ROS-sensitive signaling. Small 12:4404–4411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Chen R, He T et al (2016) Biomedical potential of ultrafine Ag/AgCl nanoparticles coated on graphene with special reference to antimicrobial performances and burn wound healing. ACS Appl Mater Interfaces 8:15067–15075

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Xu X, Liu F et al (2017) Green synthesis of graphene nanosheets and their in vitro cytotoxicity against human prostate cancer (DU 145) cell lines. Nanomater Nanotechnol 7. https://doi.org/10.1177/1847980417702794

    Article  CAS  Google Scholar 

  • Zou L, Wang H, He B et al (2016) Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics. Theranostics 6:762–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zurutuza A, Marinelli C (2014) Challenges and opportunities in graphene commercialization. Nat Nanotechnol 9:730–734

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

CRP is grateful to DST-Nanomission, New Delhi, (SR/NM/NS-1252/2013; GAP 570) for financial support. This book chapter is partially supported by ‘CSIR-Mayo Clinic Collaboration for Innovation and Translational Research’ (CKM/CMPP-09; MLP0020) fund from CSIR, New Delhi and 12th Five Year Plan (FYP) projects (ADD: CSC0302) CSIR, New Delhi, to CRP. A.K.B. and S.D. are thankful to UGC, New Delhi while A.R. and K.B. are thankful to ICMR, New Delhi, for their fellowships. The authors are thankful to the Director, CSIR-IICT for his support and encouragement and for his keen interest in this work. IICT manuscript communication number IICT/Pubs./2019/147 dated April 15, 2019 for this manuscript is duly acknowledged.

Author information

Authors and Affiliations

  1. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India

    Ayan Kumar Barui, Arpita Roy, Sourav Das, Keerti Bhamidipati & Chitta Ranjan Patra

  2. Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India

    Arpita Roy, Keerti Bhamidipati & Chitta Ranjan Patra

Authors
  1. Ayan Kumar Barui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arpita Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sourav Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keerti Bhamidipati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chitta Ranjan Patra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chitta Ranjan Patra .

Editor information

Editors and Affiliations

  1. Physics Department, Ewing Christian College, Prayagraj, Uttar Pradesh, India

    Ashutosh Kumar Shukla

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Barui, A.K., Roy, A., Das, S., Bhamidipati, K., Patra, C.R. (2020). Therapeutic Applications of Graphene Oxides in Angiogenesis and Cancers. In: Shukla, A. (eds) Nanoparticles and their Biomedical Applications. Springer, Singapore. https://doi.org/10.1007/978-981-15-0391-7_6

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-0391-7_6

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-0390-0

  • Online ISBN: 978-981-15-0391-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation