Graphene Quantum Dots in Cancer Diagnostics and Therapeutics: Advances in Biosensing, Imaging, and Treatment Applications

Abstract

Graphene quantum dots (GQDs) have emerged as promising nanomaterials in cancer therapy because of their unique physicochemical properties. This review comprehensively analyzes the roles of GQDs in cancer diagnostics and treatment, highlighting their biocompatibility, tunable photoluminescence, and surface functionalization capabilities. GQDs exhibit minimal toxicity, efficient cellular uptake, and favorable biodistribution, making them suitable for targeted drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT). Their intrinsic fluorescence also enables real-time bioimaging, supporting theranostic applications. This study explores their mechanisms of action, including reactive oxygen species (ROS) generation, heat-induced ablation, and pH-responsive drug release. GQDs have demonstrated efficacy across various cancers, such as breast, lung, brain, liver, and pancreatic cancers, through enhanced drug/gene delivery, biosensing, and image-guided therapy. Despite encouraging preclinical results, challenges related to toxicity profiling, standardization, regulatory frameworks, and scalability remain significant barriers to clinical translation. This review emphasizes the therapeutic versatility of GQDs and underscores the need for further research to overcome translational hurdles and realize their full potential in personalized cancer care.

Keywords

Graphene quantum dots (GQDs) / Nanomaterial / Cancer therapy / Drug delivery / Breast cancer / Lung cancer / Brain tumors

References

[1] Bray F, Laversanne M, Sung H, et al.. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin., 2024, 74(3): 229-263

[2] Liu B, Zhou H, Tan L, et al.. Exploring treatment options in cancer: Tumor treatment strategies. Signal Transduct Target Ther., 2024, 9(1): 175

[3] Hanmante PS, Lohiya RT, Wankhede AG, et al.. Quantum dot nanotechnology: Advancing target drug delivery in Oncology. Next Nanotechnol., 2025, 7 100172

[4] Dar MS, Sahu NK. Graphene quantum dot-crafted nanocomposites: shaping the future landscape of biomedical advances. Discov Nano., 2024, 19(179

[5] Huang Y, Wang D, Wei Y, et al.. Advances in synthesis of the graphene quantum dots from varied raw materials. Arab J Chem., 2024, 17(2 105533

[6] Gozali Balkanloo P, Mohammad Sharifi K, Poursattar Marjani A. Graphene quantum dots: synthesis, characterization, and application in wastewater treatment: a review. Mater Adv., 2023, 4(194272-4293

[7] Cui Y, Liu L, Shi M, et al. A Review of Advances in Graphene Quantum Dots: From Preparation and Modification Methods to Application. C. 2024;10(1):7.

[8] Younis MR, He G, Lin J, et al.. Recent advances on graphene quantum dots for bioimaging applications. Front Chem., 2020, 8: 424

[9] Osorio HM, Castillo-Solís F, Barragán SY, et al.. Graphene quantum dots from natural carbon sources for drug and gene delivery in cancer treatment. Int J Mol Sci., 2024, 25(19): 10539

[10] Yang Y, Wang B, Zhang X, et al.. Activatable graphene quantum-dot-based nanotransformers for long-period tumor imaging and repeated photodynamic therapy. Adv Mater., 2023, 35(232211337

[11] Zarepour A, Khosravi A, Yücel Ayten N, et al.. Innovative approaches for cancer treatment: graphene quantum dots for photodynamic and photothermal therapies. J Mater Chem B., 2024, 12(184307-4334

[12] Cao Y, Dong H, Yang Z, et al.. Aptamer-conjugated graphene quantum dots/porphyrin derivative theranostic agent for intracellular cancer-related microRNA detection and fluorescence-guided photothermal/photodynamic synergetic therapy. ACS Appl Mater Interfaces., 2017, 9(1159-166

[13] Tade RS, Patil PO. Theranostic prospects of graphene quantum dots in breast cancer. ACS Biomater Sci Eng., 2020, 6(11): 5987-6008

[14] Saadh MJ, Ballal S, Kumar A, et al.. Advances in synthesis and characterization of GQDs for enhanced photocatalytic degradation of contaminants: a comprehensive review. Inorg Chem Commun., 2024, 169 113072

[15] Peng J, Gao W, Gupta BK, et al.. Graphene quantum dots derived from carbon fibers. Nano Lett., 2012, 12(2): 844-849

[16] Liu R, Wu D, Feng X, et al.. Bottom-up fabrication of photoluminescent graphene quantum dots with uniform morphology. J Am Chem Soc., 2011, 133(39): 15221-15223

[17] Sun XD, Liu ZQ, Yan H. Preparation of graphene quantum dots and their biological applications. J Inorg Mater., 2016, 31(4): 337

[18] Hu S, Liu J, Yang J, et al.. Laser synthesis and size tailor of carbon quantum dots. J Nanopart Res., 2011, 13(127247-7252

[19] Fan T, Zeng W, Tang W, et al.. Controllable size-selective method to prepare graphene quantum dots from graphene oxide. Nanoscale Res Lett., 2015, 10: 55

[20] Dervishi E, Ji Z, Htoon H, et al.. Raman spectroscopy of bottom-up synthesized graphene quantum dots: size and structure dependence. Nanoscale., 2019, 11(35): 16571-16581

[21] Liang L, Kong Z, Kang Z, et al.. Theoretical evaluation on potential cytotoxicity of graphene quantum dots. ACS Biomater Sci Eng., 2016, 2(111983-1991

[22] Wu C, Wang C, Han T, et al.. Insight into the cellular internalization and cytotoxicity of graphene quantum dots. Adv Healthc Mater., 2013, 2(12): 1613-1619

[23] Shang YD, Chen XH, Ma WH, et al.. Preparation and optical properties research on graphene quantum dots. Key Eng Mater., 2017, 727: 303-308

[24] Choudhary RP, Shukla S, Vaibhav K, et al.. Optical properties of few layered graphene quantum dots. Mater Res Express., 2015, 2(9 095024

[25] Ozfidan I, Güçlü AD, Korkusinski M, et al.. Theory of optical properties of graphene quantum dots. Phys Status Solidi RRL., 2016, 10(1): 102-110

[26] Mukhopadhyay M, Pandey B, Pati SK. Tuning the optically bright and dark states of doped graphene quantum dots. Phys Rev Applied., 2016, 6(4 044014

[27] Shafraniuk SE. Unconventional electromagnetic properties of the graphene quantum dots. Phys Rev B., 2019, 100(7 075404

[28] Wang X, Li Y, Song P, et al.. Second-order nonlinear optical switch manipulation of photosensitive layer by an external electric field coupled with graphene quantum dots. J Phys Chem A., 2019, 123(34): 7401-7407

[29] Klekachev AV, Cantoro M, van der Veen MH, et al.. Electron accumulation in graphene by interaction with optically excited quantum dots. Phys E Low Dimension Syst Nanostruct., 2011, 43(5): 1046-1049

[30] Shinde S, Patil A, Gaikwad R. Graphene quantum dots: a pharmaceutical review. Asian J Pharm Res. 2022:341–348.

[31] Faridbod F, Sanati AL. Graphene quantum dots in electrochemical sensors/biosensors. Curr Anal Chem., 2019, 15(2): 103-123

[32] Lu H, Li W, Dong H, et al.. Graphene quantum dots for optical bioimaging. Small., 2019, 15(36): 1902136

[33] Zhang R, Ding Z. Recent advances in graphene quantum dots as bioimaging probes. J Anal Test., 2018, 2(145-60

[34] Hadad C, González-Domínguez JM, Armelloni S, et al.. Graphene quantum dots: From efficient preparation to safe renal excretion. Nano Res., 2021, 14(3): 674-683

[35] Henna TK, Pramod K. Biocompatibility of graphene quantum dots and related materials. Handbook of Biomaterials Biocompatibility. Amsterdam: Elsevier, 2020:353–367.

[36] Sengupta S, Pal S, Pal A, et al.. A review on synthesis, toxicity profile and biomedical applications of graphene quantum dots (GQDs). Inorg Chim Acta., 2023, 557 121677

[37] Singh H, Sreedharan S, Tiwari K, et al.. Two photon excitable graphene quantum dots for structured illumination microscopy and imaging applications: lysosome specificity and tissue-dependent imaging. Chem Commun (Camb)., 2019, 55(4): 521-524

[38] Marković Z, Dorontić S, Jovanović S, et al.. Biocompatible carbon dots/polyurethane composites as potential agents for combating bacterial biofilms: N-doped carbon quantum dots/polyurethane and gamma ray-modified graphene quantum dots/polyurethane composites. Pharmaceutics., 2024, 16(12): 1565

[39] Ribeiro ERFR, Correa LB, Ricci-Junior E, et al.. Chitosan-graphene quantum dot based active film as smart wound dressing. J Drug Deliv Sci Technol., 2023, 80 104093

[40] Barua S, Rege K. Cancer-cell-phenotype-dependent differential intracellular trafficking of unconjugated quantum dots. Small., 2009, 5(3370-376

[41] Karabanovas V, Zitkus Z, Kuciauskas D, et al.. Surface properties of quantum dots define their cellular endocytic routes, mitogenic stimulation and suppression of cell migration. J Biomed Nanotechnol., 2014, 10(5): 775-786

[42] Kersting D, Fasbender S, Pilch R, et al.. From in vitro to ex vivo: subcellular localization and uptake of graphene quantum dots into solid tumors. Nanotechnology., 2019, 30(39 395101

[43] Zheng S, Jin Z, Han C, et al.. Graphene quantum dots-decorated hollow copper sulfide nanoparticles for controlled intracellular drug release and enhanced photothermal-chemotherapy. J Mater Sci., 2020, 55(3): 1184-1197

[44] Chen X, Fan Y, Sun J, et al.. Nanoparticle-mediated specific elimination of soft cancer stem cells by targeting low cell stiffness. Acta Biomater., 2021, 135: 493-505

[45] Dash BS, Lu YJ, Chen JP. Enhancing photothermal/photodynamic therapy for glioblastoma by tumor hypoxia alleviation and heat shock protein inhibition using IR820-conjugated reduced graphene oxide quantum dots. ACS Appl Mater Interfaces., 2024, 16(11): 13543-13562

[46] Lin J, Chen X, Huang P. Graphene-based nanomaterials for bioimaging. Adv Drug Deliv Rev., 2016, 105(Pt B): 242-254

[47] Kadian S, Manik G, Das N, et al.. Targeted bioimaging and sensing of folate receptor-positive cancer cells using folic acid-conjugated sulfur-doped graphene quantum dots. Microchim Acta., 2020, 187(8): 458

[48] Omidian H, Wilson RL, Cubeddu LX. Quantum dot research in breast cancer: challenges and prospects. Materials (Basel)., 2024, 17(92152

[49] Kunachowicz D, Kłosowska K, Sobczak N, et al.. Applicability of quantum dots in breast cancer diagnostic and therapeutic modalities—a state-of-the-art review. Nanomaterials., 2024, 14(171424

[50] Tan YY, Yap PK, Xin Lim GL, et al.. Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics. Chem Biol Interact., 2020, 329 109221

[51] Valimukhametova AR, Lee BH, Topkiran UC, et al.. Cancer therapeutic siRNA delivery and imaging by nitrogen- and neodymium-doped graphene quantum dots. ACS Biomater Sci Eng., 2023, 9(63425-3434

[52] Zhang W, Sigdel G, Mintz KJ, et al.. Carbon dots: a future blood-brain barrier penetrating nanomedicine and drug nanocarrier. Int J Nanomedicine., 2021, 16: 5003-5016

[53] Chan MH, Huang WT, Satpathy A, et al.. Progress and viewpoints of multifunctional composite nanomaterials for glioblastoma theranostics. Pharmaceutics., 2022, 14(2): 456

[54] Perini G, Palmieri V, Ciasca G, et al.. Enhanced chemotherapy for glioblastoma multiforme mediated by functionalized graphene quantum dots. Materials (Basel)., 2020, 13(184139

[55] Chen L, Hong W, Duan S, et al.. Graphene quantum dots mediated magnetic chitosan drug delivery nanosystems for targeting synergistic photothermal-chemotherapy of hepatocellular carcinoma. Cancer Biol Ther., 2022, 23(1281-293

[56] Metkar SP, Fernandes G, Navti PD, et al.. Nanoparticle drug delivery systems in hepatocellular carcinoma: a focus on targeting strategies and therapeutic applications. OpenNano., 2023, 12 100159

[57] Yin X, Rong J, Shao M, et al.. Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma. J Nanobiotechnol., 2024, 22(1): 243

[58] Graur F, Puia A, Mois EI, et al.. Nanotechnology in the diagnostic and therapy of hepatocellular carcinoma. Materials (Basel)., 2022, 15(113893

[59] Hu X, Xia F, Lee J, et al.. Tailor-made nanomaterials for diagnosis and therapy of pancreatic ductal adenocarcinoma. Adv Sci (Weinh)., 2021, 8(72002545

[60] Fathi-karkan S, Sargazi S, Shojaei S, et al.. Biotin-functionalized nanoparticles: an overview of recent trends in cancer detection. Nanoscale., 2024, 16(2712750-12792

[61] Zhang J, Ding H, Zhang F, et al.. New trends in diagnosing and treating ovarian cancer using nanotechnology. Front Bioeng Biotechnol., 2023, 11: 1160985

[62] Nedelcu A, Mocan T, Grapa C, et al.. Recent advances in nanoparticle-mediated diagnosis and the treatment of pancreatic cancer. Int J Mol Sci., 2021, 22(15): 8060

[63] Ghanbari N, Salehi Z, Ali Khodadadi A, et al.. Glucosamine-conjugated graphene quantum dots as versatile and pH-sensitive nanocarriers for enhanced delivery of curcumin targeting to breast cancer. Mater Sci Eng C., 2021, 121 111809

[64] Ko NR, Nafiujjaman M, Lee JS, et al.. Graphene quantum dot-based theranostic agents for active targeting of breast cancer. RSC Adv., 2017, 7(1911420-11427

[65] Dar MS, Rosaiah P, Bhagyalakshmi J, et al.. Graphene quantum dots as nanotherapeutic agents for triple-negative breast cancer: Insights from 3D tumor models. Coord Chem Rev., 2025, 523 216247

[66] Ku TH, Shen WT, Hsieh CT, et al.. Specific forms of graphene quantum dots induce apoptosis and cell cycle arrest in breast cancer cells. Int J Mol Sci., 2023, 24(44046

[67] Morani DO, Patil PO. Review on Multifunctional Nanotherapeutics for Drug Delivery, Tumor Imaging, and Selective Tumor Targeting by Hyaluronic Acid Coupled Graphene Quantum Dots. Curr Nanosci., 2024, 20(189-108

[68] Li R, Wang X, Li Z, et al.. Folic acid-functionalized graphene quantum dots with tunable fluorescence emission for cancer cell imaging and optical detection of Hg²⁺. New J Chem., 2018, 42(6): 4352-4360

[69] Havanur S, Batish I, Cheruku SP, et al.. Poly(N, N-diethyl acrylamide)/functionalized graphene quantum dots hydrogels loaded with doxorubicin as a nano-drug carrier for metastatic lung cancer in mice. Mater Sci Eng C., 2019, 105 110094

[70] Kang SH, Lee JY, Kim SK, et al.. Graphene quantum dots-loaded macrophages as a biomimetic delivery system for bioimaging and photodynamic therapy. J Drug Deliv Sci Technol., 2023, 85 104620

[71] Tung FI, Zheng LJ, Hou KT, et al.. One-stop radiotherapeutic targeting of primary and distant osteosarcoma to inhibit cancer progression and metastasis using 2DG-grafted graphene quantum dots. Nanoscale., 2020, 12(16): 8809-8818

[72] Kalkal A, Pradhan R, Kadian S, et al.. Biofunctionalized graphene quantum dots based fluorescent biosensor toward efficient detection of small cell lung cancer. ACS Appl Bio Mater., 2020, 3(8): 4922-4932

[73] Tade RS, Patil PO. Biofabricated functionalized graphene quantum dots (fGQDs): unraveling its fluorescence sensing mechanism of human telomerase reverse transcriptase (hTERT) antigen and in vitro bioimaging application. Biomed Mater., 2022, 17 055010

[74] Wang C, Chen Y, Xu Z, et al.. Fabrication and characterization of novel cRGD modified graphene quantum dots for chemo-photothermal combination therapy. Sens Actuat B Chem., 2020, 17(5 127732

[75] Kulkarni NS, Parvathaneni V, Shukla SK, et al.. Tyrosine kinase inhibitor conjugated quantum dots for non-small cell lung cancer (NSCLC) treatment. Eur J Pharm Sci., 2019, 133: 145-159

[76] Perini G, Palmieri V, Ciasca G, et al.. Graphene quantum dots’ surface chemistry modulates the sensitivity of glioblastoma cells to chemotherapeutics. Int J Mol Sci., 2020, 21(17): 6301

[77] Perini G, Palmieri V, Ciasca G, et al. Functionalized graphene quantum dots modulate malignancy of glioblastoma multiforme by downregulating neurospheres formation. C. 2021;7(1):4.

[78] Lu YJ, Vayalakkara RK, Dash BS, et al.. Immunomodulatory R848-loaded anti-PD-L1-conjugated reduced graphene oxide quantum dots for photothermal immunotherapy of glioblastoma. Pharmaceutics., 2024, 16(81064

[79] Mazaheri Tehrani M, Erfani M, Amiri M, et al.. Technetium-99m radiolabeling of graphene quantum dots (GQDs) as a new probe for glioblastoma tumor imaging. Int J Radiat Biol., 2025, 101(165-72

[80] Nangare S, Chandankar S, Patil P. Design of carbon and graphene quantum dots based nanotheranostics applications for glioblastoma management: Recent advanced and future prospects. J Drug Deliv Sci Technol., 2023, 89 105060

[81] Chavda V, Patel V, Yadav D, et al.. Therapeutics and research related to glioblastoma: advancements and future targets. Curr Drug Metab., 2020, 21(3): 186-198

[82] Nigam P, Waghmode S, Louis M, et al.. Graphene quantum dots conjugated albumin nanoparticles for targeted drug delivery and imaging of pancreatic cancer. J Mater Chem B., 2014, 2(21): 3190-3195

[83] Kumar Shukla M, Parihar A, Karthikeyan C, et al.. Multifunctional GQDs for receptor targeting, drug delivery, and bioimaging in pancreatic cancer. Nanoscale., 2023, 15(36): 14698-14716

[84] Nigam Joshi P, Agawane S, Athalye MC, et al.. Multifunctional inulin tethered silver-graphene quantum dots nanotheranostic module for pancreatic cancer therapy. Mater Sci Eng C., 2017, 78: 1203-1211

[85] Yang C, Chan KK, Xu G, et al.. Biodegradable polymer-coated multifunctional graphene quantum dots for light-triggered synergetic therapy of pancreatic cancer. ACS Appl Mater Interfaces., 2019, 11(3): 2768-2781

[86] Ajgaonkar R, Lee B, Valimukhametova A, et al.. Detection of pancreatic cancer miRNA with biocompatible nitrogen-doped graphene quantum dots. Materials., 2022, 15(16): 5760

[87] Joshi P, Waghmode S. Graphene quantum dot-based on-chip electrochemical DNA hybridization sensor for pancreatic cancer. Rep Electrochem., 2016, 6: 31-40

[88] Qi L, Pan T, Ou L, et al.. Biocompatible nucleus-targeted graphene quantum dots for selective killing of cancer cells via DNA damage. Commun Biol., 2021, 4: 214

[89] Nurunnabi M, Khatun Z, Huh KM, et al.. In vivo biodistribution and toxicology of carboxylated graphene quantum dots. ACS Nano., 2013, 7(86858-6867

[90] Chong Y, Ma Y, Shen H, et al.. The in vitro and in vivo toxicity of graphene quantum dots. Biomaterials., 2014, 35(195041-5048

[91] Yang Y, Lima RC, Gemini-Piperni S, et al.. Graphene quantum dots for molecular radiotherapy: radiolabeled graphene quantum dots with radium (²²³Ra) showed potent effect against bone cancer. J Biomed Nanotechnol., 2021, 17(9): 1858-1865

[92] Nafiujjaman M, Joon H, Kwak K, et al.. Synthesis of Nitrogen- and Chlorine-Doped Graphene Quantum Dots for Cancer Cell Imaging. J Nanosci Nanotechnol., 2017, 18(7): 3793-3799

[93] Yao C, Tu Y, Ding L, et al.. Tumor cell-specific nuclear targeting of functionalized graphene quantum dots in vivo. Bioconjug Chem., 2017, 28(10): 2608-2619

[94] Lo PY, Lee GY, Zheng JH, et al.. GFP plasmid and chemoreagent conjugated with graphene quantum dots as a novel gene delivery platform for colon cancer inhibition in vitro and in vivo. ACS Appl Bio Mater., 2020, 3(9): 5948-5956

[95] Ramana LN, Dinh LNM, Agarwal V. Influence of surface charge of graphene quantum dots on their uptake and clearance in melanoma cells. Nanoscale Adv., 2021, 3(12): 3513-3521

[96] Peynshaert K, Soenen SJ, Manshian BB, et al.. Coating of Quantum Dots strongly defines their effect on lysosomal health and autophagy. Acta Biomater., 2017, 48: 195-205

[97] Arab K, Jafari A, Shahi F. The role of graphene quantum dots in cutting-edge medical therapies. Polym Adv Technol., 2024, 35(9 e6571

[98] Iannazzo D, Celesti C, Espro C. Recent advances on graphene quantum dots as multifunctional nanoplatforms for cancer treatment. Biotechnol J., 2021, 16(2 e1900422

[99] Kadian S, Shukla S, Yadav AK, et al.. Recent advancements in graphene quantum dot-based bioimaging and drug delivery systems. MedComm., 2025, 6(10 e70320

[100] Chen J, Li B, Liu D, et al.. Single-molecule graphene quantum dots: enhancement of optical properties and promotion of photodynamic efficacy based on precise control of the electronic structure. Chem Sci., 2025, 16(40): 18806-18820

[101] Bhattacharya T, Preetam S, Mukherjee S, et al.. Anticancer activity of quantum size carbon dots: opportunities and challenges. Discov Nano., 2024, 19(1): 122

[102] Khodadadei F, Safarian S, Ghanbari N. Methotrexate-loaded nitrogen-doped graphene quantum dots nanocarriers as an efficient anticancer drug delivery system. Mater Sci Eng C., 2017, 79: 280-285

[103] Bas TG. Innovative formulation strategies for biosimilars: trends focused on buffer-free systems, safety, regulatory alignment, and intellectual property challenges. Pharmaceuticals., 2025, 18(6908

[104] Zheng M, Li W, Ma F, et al.. Graphitic carbon nitride-based materials: applications in medical diagnostics, therapeutics, and combined cancer therapies. J Mater Chem C., 2025, 13(3417483-17536

[105] Zhou J, Huang J, Chen H, et al.. Low-cost synthesis of silicon quantum dots with near-unity internal quantum efficiency. J Phys Chem Lett., 2021, 12(37): 8909-8916

[106] Kohli HK, Parab D. Green synthesis of carbon quantum dots and applications: an insight. Next Mater., 2025, 8 100527

[107] Adegoke MF, Daramola OA, Adeniyi KO, et al.. Toxicity evaluation of pharmaceutical drugs and quantum dots (QDs) using zebrafish embryos–A comprehensive review. SLAS Discov., 2025, 35 100241

[108] Alavi SE, Alharthi S, Alavi SF, et al.. Microfluidics for personalized drug delivery. Drug Discov Today., 2024, 29(4 103936

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology

Just Accepted

This article has successfully passed peer review and final editorial review, and will soon enter typesetting, proofreading and other publishing processes. The currently displayed version is the accepted final manuscript. The officially published version will be updated with format, DOI and citation information upon launch. We recommend that you pay attention to subsequent journal notifications and preferentially cite the officially published version. Thank you for your support and cooperation.