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Carbon dots and composite materials with excellent performances in cancer-targeted bioimaging and killing: a review

    Chenggang Wang‡

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    Key Laboratory of Dental Maxillofacial Reconstruction & Biological Intelligence Manufacturing of Gansu Province, Lanzhou University, Lanzhou, 730000, PR China

    ‡Authors contributed equally to this work

    Search for more papers by this author

    ,
    Lixin Chen‡

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ‡Authors contributed equally to this work

    Search for more papers by this author

    ,
    Rongshuang Tan

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ,
    Yuchen Li

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ,
    Yiqing Zhao

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ,
    Lingzi Liao

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ,
    Zhangjie Ge

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ,
    Chuanyang Ding

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    ,
    Zhankui Xing

    *Author for correspondence:

    E-mail Address: xingzhk12@lzu.edu.cn

    The Second Hospital of Lanzhou University, Lanzhou, 730030, PR China

    &
    Ping Zhou

    **Author for correspondence:

    E-mail Address: zhoup@lzu.edu.cn

    School & Hospital of Stomatology, Lanzhou University, Lanzhou, 730000, PR China

    Key Laboratory of Dental Maxillofacial Reconstruction & Biological Intelligence Manufacturing of Gansu Province, Lanzhou University, Lanzhou, 730000, PR China

    Published Online:https://doi.org/10.2217/nnm-2023-0216

    Carbon dots (CDs) are nanomaterials with excellent properties, including good biocompatibility, small size, ideal photoluminescence and surface modification, and are becoming one of the most attractive nanomaterials for the imaging, detection and treatment of tumors. Based on these advantages, CDs can be combined other materials to obtain composite particles with improved, even new, performance, mainly in photothermal and photodynamic therapies. This paper reviews the research progress of CDs and their composites in targeted tumor imaging, detection, diagnosis, drug delivery and tumor killing. It also discusses and proposes the challenges and perspectives of their future applications in these fields. This review provides ideas for future applications of novel CD-based materials in the diagnosis and treatment of cancer.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Hu XJ, Zhu ZK, Dong HB et al. Inorganic and metal–organic nanocomposites for cascade-responsive imaging and photochemical synergistic effects. Inorg. Chem. 59(7), 4617–4625 (2020).
    • 2. Chan MH, Chang ZX, Huang CF, Lee LJ, Liu RS, Hsiao M. Integrated therapy platform of exosomal system: hybrid inorganic/organic nanoparticles with exosomes for cancer treatment. Nanoscale Horiz. 7(4), 352–367 (2022).
    • 3. Son J, Yi G, Yoo J, Park C, Koo H, Choi HS. Light-responsive nanomedicine for biophotonic imaging and targeted therapy. Adv. Drug Deliv. Rev. 138, 133–147 (2019).
    • 4. Luo H, Gao S. Recent advances in fluorescence imaging-guided photothermal therapy and photodynamic therapy for cancer: from near-infrared-I to near-infrared-II. J. Control. Rel. 362, 425–445 (2023).
    • 5. Pirsaheb M, Mohammadi S, Salimi A, Payandeh M. Functionalized fluorescent carbon nanostructures for targeted imaging of cancer cells: a review. Microchim. Acta 186(4), 231 (2019).
    • 6. Hashemi F, Heidari F, Mohajeri N, Mahmoodzadeh F, Zarghami N. Fluorescence intensity enhancement of green carbon dots: synthesis, characterization and cell imaging. Photochem. Photobiol. 96(5), 1032–1040 (2020).
    • 7. Bhosale SR, Bhosale RR, Patil DN et al. Bioderived mesoporous carbon@tungsten oxide nanocomposite as a drug carrier vehicle of doxorubicin for potent cancer therapy. Langmuir 39(33), 11910–11924 (2023).
    • 8. Prieto-Montero R, Katsumiti A, Cajaraville MP, López-Arbeloa I, Martínez-Martínez V. Functionalized fluorescent silica nanoparticles for bioimaging of cancer cells. Sensors 20(19), 5590 (2020).
    • 9. Du XF, Zhu BJ, Cai ZC, Wang C, Zhao MX. Polyamine-modified gold nanoparticles readily adsorb on cell membranes for bioimaging. ACS Omega 4(18), 17850–17856 (2019).
    • 10. Ge W, Zhang YY, Ye J et al. Facile synthesis of fluorescent Au/Ce nanoclusters for high-sensitive bioimaging. J. Nanobiotechnol. 13, 8 (2015).
    • 11. Min H, Qi YQ, Chen YH et al. Synthesis and imaging of biocompatible graphdiyne quantum dots. ACS Appl. Mater. Interfaces 11(36), 32798–32807 (2019).
    • 12. Zhang Y, Han L, Zhang Y et al. Glutathione-mediated mesoporous carbon as a drug delivery nanocarrier with carbon dots as a cap and fluorescent tracer. Nanotechnology 27(35), 355102 (2016).
    • 13. Yoon HY, Jeon S, You DG et al. Inorganic nanoparticles for image-guided therapy. Bioconjugate Chem. 28(1), 124–134 (2017).
    • 14. Cha BG, Kim J. Functional mesoporous silica nanoparticles for bio-imaging applications. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 11(1), e1515 (2019).
    • 15. Li SH, Wei XD, Li SS, Zhu CM, Wu CH. Up-conversion luminescent nanoparticles for molecular imaging, cancer diagnosis and treatment. Int. J. Nanomed. 15, 9431–9445 (2020).
    • 16. Nguyen PD, Son SJ, Min J. Upconversion nanoparticles in bioassays, optical imaging and therapy. J. Nanosci. Nanotechnol. 14(1), 157–174 (2014).
    • 17. Alkahtani MH, Fahad A, Jiang L et al. Fluorescent nanodiamonds: past, present, and future. Nanophotonics 7(8), 1423–1453 (2018).
    • 18. Majdalawieh A, Kanan MC, El-Kadri O, Kanan SM. Recent advances in gold and silver nanoparticles: synthesis and applications. J. Nanosci. Nanotechnol. 14(7), 4757–4780 (2014).
    • 19. Gao XH, Cui YY, Levenson RM, Chung LW, Nie SM. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22(8), 969–976 (2004).
    • 20. Phan LMT, Cho S. Fluorescent carbon dot-supported imaging-based biomedicine: a comprehensive review. Bioinorg. Chem. Appl. 2022, 9303703 (2022).
    • 21. Nocito G, Calabrese G, Forte S et al. Carbon dots as promising tools for cancer diagnosis and therapy. Cancers (Basel) 13(9), 1991 (2021).
    • 22. Xu XY, Ray R, Gu YL et al. Electrophoretic analysis and purification of fluorescent single-walled carbon nanotube fragments. J. Am. Chem. Soc. 126(40), 12736–12737 (2004).
    • 23. Ostadhossein F, Pan D. Functional carbon nanodots for multiscale imaging and therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 9(3), doi: 10.1002/wnan.1436 (2017).
    • 24. Anand A, Manavalan G, Mandal RP, Chang HT, Chiou YR, Huang CC. Carbon dots for bacterial detection and antibacterial applications – a minireview. Curr. Pharm. Des. 25(46), 4848–4860 (2019).
    • 25. Du JJ, Xu N, Fan JL, Sun W, Peng JX. Carbon dots for in vivo bioimaging and theranostics. Small 15(32), e1805087 (2019).
    • 26. Rawat P, Nain P, Sharma S et al. An overview of synthetic methods and applications of photoluminescence properties of carbon quantum dots. Luminescence 38(7), 845–866 (2023).
    • 27. Baker SN, Baker GA. Luminescent carbon nanodots: emergent nanolights. Angew. Chem. Int. Ed. Engl. 49(38), 6726–6744 (2010).
    • 28. Wang SJ, Wang BB, Bai FW, Ma XJ. Tumor cell responses to carbon dots derived from chondroitin sulfate. RSC Adv. 5(99), 81388–81394 (2015).
    • 29. Kang ZH, Lee ST. Carbon dots: advances in nanocarbon applications. Nanoscale 11(41), 19214–19224 (2019).
    • 30. Thangaraj B, Solomon PR, Ranganathan S. Synthesis of carbon quantum dots with special reference to biomass as a source – a review. Curr. Pharm. Des. 25(13), 1455–1476 (2019).
    • 31. Mishra V, Patil A, Thakur S, Kesharwani P. Carbon dots: emerging theranostic nanoarchitectures. Drug Discov. Today 23(6), 1219–1232 (2018).
    • 32. Liu JH, Yang ST, Chen XX, Wang H. Fluorescent carbon dots and nanodiamonds for biological imaging: preparation, application, pharmacokinetics and toxicity. Curr. Drug Metab. 13(8), 1046–1056 (2012).
    • 33. Pan DY, Zhang JC, Li Z, Zhang ZW, Guo L, Wu MH. Blue fluorescent carbon thin films fabricated from dodecylamine-capped carbon nanoparticles. J. Mater. Chem. 21(11), 3565–3567 (2011).
    • 34. Mohandoss S, Palanisamy S, You S, Shim J-J, Lee YR. Rapid detection of silver ions based on luminescent carbon nanodots for multicolor patterning, smartphone sensors, and bioimaging applications. Anal. Methods 13(47), 5719–5726 (2021).
    • 35. Kaur N, Tiwari P, Kumar P, Biswas M, Sonawane A, Mobin SM. Multifaceted carbon dots: toward pH-responsive delivery of 5-fluorouracil for in vitro antiproliferative activity. ACS Appl. Bio. Mater. 6(7), 2760–2770 (2023).
    • 36. Anpalagan K, Karakkat JV, Jelinek R et al. A green synthesis route to derive carbon quantum dots for bioimaging cancer cells. Nanomaterials (Basel) 13(14), 2103 (2023).
    • 37. Chandra A, Deshpande S, Shinde DB, Pillai VK, Singh N. Mitigating the cytotoxicity of graphene quantum dots and enhancing their applications in bioimaging and drug delivery. ACS Macro Lett. 3(10), 1064–1068 (2014).
    • 38. Jiang L, Cai H, Qin W, Li Z, Zhang L, Bi H. Meticulously designed carbon dots as photo-triggered RNA-destroyer for evoking pyroptosis. Bioconjugate Chem. 34(8), 1387–1397 (2023).
    • 39. Wen Y, Jia Q, Nan F et al. Pheophytin derived near-infrared-light responsive carbon dot assembly as a new phototheranotic agent for bioimaging and photodynamic therapy. Chemistry 14(12), 2162–2168 (2019).
    • 40. Malavika JP, Shobana C, Sundarraj S, Ganeshbabu M, Kumar P, Selvan RK. Green synthesis of multifunctional carbon quantum dots: an approach in cancer theranostics. Biomater. Adv. doi: 10.1016/j.bioadv.2022.212756 (2022) (Epub ahead of print).
    • 41. Sonaimuthu M, Ganesan S, Anand S et al. Multiple heteroatom dopant carbon dots as a novel photoluminescent probe for the sensitive detection of Cu2+ and Fe3+ ions in living cells and environmental sample analysis. Environ. Res. 219, 115106 (2023).
    • 42. Sun YP, Zhou B, Lin Y et al. Quantum-sized carbon dots for bright and colorful photoluminescence. J. Am. Chem. Soc. 128(24), 7756–7757 (2006).
    • 43. Arcudi F, Dordevic L, Prato M. Rationally designed carbon nanodots towards pure white-light emission. Angew. Chem. Int. Ed. Engl. 56(15), 4170–4173 (2017).
    • 44. Zhang J, Yuan Y, Liang GL, Yu SH. Scale-up synthesis of fragrant nitrogen-doped carbon dots from bee pollens for bioimaging and catalysis. Adv. Sci. 2(4), 201500002 (2015).
    • 45. Lu SY, Xiao GJ, Sui LZ et al. Piezochromic carbon dots with two-photon fluorescence. Angew. Chem. Int. Ed. Engl. 56(22), 6187–6191 (2017).
    • 46. Bao L, Liu C, Zhang ZL, Pang DW. Photoluminescence-tunable carbon nanodots: surface-state energy-gap tuning. Adv. Mater. 27(10), 1663–1667 (2015).
    • 47. Gan ZX, Wu XL, Zhou GX, Shen JC, Chu PK. Is there real upconversion photoluminescence from graphene quantum dots? Adv. Opt. Mater. 1(8), 554–558 (2013).
    • 48. Jiang Y, Tan Z, Zhao T et al. Indocyanine green derived carbon dots with significantly enhanced properties for efficient photothermal therapy. Nanoscale 15(4), 1925–1936 (2023).
    • 49. Ci QQ, Wang YY, Wu B et al. Fe-doped carbon dots as NIR-II fluorescence probe for in vivo gastric imaging and pH detection. Adv. Sci. 10(7), e2206271 (2023). • An interesting study of carbon dots for in vivo NIR-II bio-imaging and deep in vivo pH monitoring.
    • 50. Li H, Yan X, Kong D et al. Recent advances in carbon dots for bioimaging applications. Nanoscale Horiz. 5(2), 218–234 (2020).
    • 51. Mohandoss S, Ahmad N, Khan MR et al. Nitrogen and sulfur co-doped photoluminescent carbon dots for highly selective and sensitive detection of Ag+ and Hg2+ ions in aqueous media: applications in bioimaging and real sample analysis. Environ. Res. 228, 115898 (2023).
    • 52. Mohandoss S, Palanisamy S, Priya VV et al. Excitation-dependent multiple luminescence emission of nitrogen and sulfur co-doped carbon dots for cysteine sensing, bioimaging, and photoluminescent ink applications. Microchem. J. 167, 106280 (2021).
    • 53. Mohandoss S, Khanal HD, Palanisamy S, You S, Shim J-J, Lee YR. Multiple heteroatom-doped photoluminescent carbon dots for ratiometric detection of Hg2+ ions in cell imaging and environmental applications. Anal. Methods 14(6), 635–642 (2022).
    • 54. Mohandoss S, Ahmad N, Rizwan Khan M et al. Multicolor emission-based nitrogen, sulfur and boron co-doped photoluminescent carbon dots for sequential sensing of Fe3+ and cysteine: RGB color sensor and live cell imaging. Spectrochim. Acta A Mol. Biomol. Spectrosc. 302, 123040 (2023).
    • 55. Mohandoss S, Ganesan S, Palanisamy S et al. Nitrogen, sulfur, and phosphorus co-doped carbon dots-based ratiometric chemosensor for highly selective sequential detection of Al3+ and Fe3+ ions in logic gate, cell imaging, and real sample analysis. Chemosphere 313, 137444 (2023).
    • 56. Jia X, Li J, Wang E. One-pot green synthesis of optically pH-sensitive carbon dots with upconversion luminescence. Nanoscale 4(18), 5572–5575 (2012).
    • 57. Jia X, Han Y, Pei M et al. Multi-functionalized hyaluronic acid nanogels crosslinked with carbon dots as dual receptor-mediated targeting tumor theranostics. Carbohydr. Polym. 152, 391–397 (2016).
    • 58. Su Y, Liu S, Guan Y, Xie Z, Zheng M, Jing X. Renal clearable hafnium-doped carbon dots for CT/fluorescence imaging of orthotopic liver cancer. Biomaterials 255, 120110 (2020).
    • 59. Radnia F, Mohajeri N, Zarghami N. New insight into the engineering of green carbon dots: possible applications in emerging cancer theranostics. Talanta 209, 120547 (2020).
    • 60. Shan DY, Hsieh JT, Bai XC, Yang J. Citrate-based fluorescent biomaterials. Adv. Healthcare Mater. 7(18), e1800532 (2018).
    • 61. Kundu A, Lee J, Park B et al. Facile approach to synthesize highly fluorescent multicolor emissive carbon dots via surface functionalization for cellular imaging. J. Colloid Interface Sci. 513, 505–514 (2018).
    • 62. Zhang YN, Zhang XW, Shi YP, Sun C, Zhou N, Wen HX. The synthesis and functional study of multicolor nitrogen-doped carbon dots for live cell nuclear imaging. Molecules 25(2), 306 (2020).
    • 63. Gu D, Hong L, Zhang L, Liu H, Shang SM. Nitrogen and sulfur co-doped highly luminescent carbon dots for sensitive detection of Cd (II) ions and living cell imaging applications. J. Photochem. Photobiol. B 186, 144–151 (2018).
    • 64. Wu LH, Long RQ, Li T et al. One-pot fabrication of dual-emission and single-emission biomass carbon dots for Cu2+ and tetracycline sensing and multicolor cellular imaging. Anal. Bioanal. Chem. 412(27), 7481–7489 (2020).
    • 65. Shen CL, Liu HR, Lou Q et al. Recent progress of carbon dots in targeted bioimaging and cancer therapy. Theranostics 12(6), 2860–2893 (2022).
    • 66. Kumar Shukla M, Parihar A, Karthikeyan C, Kumar D, Khan R. Multifunctional GQDs for receptor targeting, drug delivery, and bioimaging in pancreatic cancer. Nanoscale 15, 14698–14716 (2023).
    • 67. Jullien L, Gautier A. Fluorogen-based reporters for fluorescence imaging: a review. Methods Appl. Fluoresc. 3(4), 42007 (2015).
    • 68. Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal. Biochem. 338(2), 284–293 (2005).
    • 69. Bhunia SK, Maity AR, Nandi S, Stepensky D, Jelinek R. Imaging cancer cells expressing the folate receptor with carbon dots produced from folic acid. Chembiochem 17(7), 614–619 (2016).
    • 70. Saljoughi H, Khakbaz F, Mahani M. Synthesis of folic acid conjugated photoluminescent carbon quantum dots with ultrahigh quantum yield for targeted cancer cell fluorescence imaging. Photodiagn. Photodyn. Ther. 30, 101687 (2020).
    • 71. Liu HF, Li ZH, Sun YQ et al. Synthesis of luminescent carbon dots with ultrahigh quantum yield and inherent folate receptor-positive cancer cell targetability. Sci. Rep. 8(1), 1086 (2018).
    • 72. Zhang JL, Zhao XW, Xian M, Dong C, Shuang SM. Folic acid-conjugated green luminescent carbon dots as a nanoprobe for identifying folate receptor-positive cancer cells. Talanta 183, 39–47 (2018).
    • 73. Wang SC, Chen L, Wang JL et al. Enhanced-fluorescent imaging and targeted therapy of liver cancer using highly luminescent carbon dots-conjugated foliate. Mater. Sci. Eng. C Mater. Biol. Appl. 116, 111233 (2020).
    • 74. Zhang HQ, Wang G, Zhang ZM et al. One step synthesis of efficient red emissive carbon dots and their bovine serum albumin composites with enhanced multi-photon fluorescence for in vivo bioimaging. Light: Sci. Appl. 11(1), 113 (2022). • A meaningful study of an efficient red light emitting carbon dots for in vivo tumor imaging in mice.
    • 75. Phan LMT, Gul AR, Le TN et al. One-pot synthesis of carbon dots with intrinsic folic acid for synergistic imaging-guided photothermal therapy of prostate cancer cells. Biomater. Sci. 7(12), 5187–5196 (2019).
    • 76. Henson E, Chen Y, Gibson S. EGFR family members' regulation of autophagy is at a crossroads of cell survival and death in cancer. Cancers (Basel) 9(4), 27 (2017).
    • 77. Demir B, Lemberger MM, Panagiotopoulou M et al. Tracking hyaluronan: molecularly imprinted polymer coated carbon dots for cancer cell targeting and imaging. ACS Appl. Mater. Interfaces 10(4), 3305–3313 (2018).
    • 78. Zhang Y, Li S, Ma XT, He XW, Li WY, Zhang YK. Carbon dots-embedded epitope imprinted polymer for targeted fluorescence imaging of cervical cancer via recognition of epidermal growth factor receptor. Microchim. Acta 187(4), 228 (2020). • An interesting study of carbon dot-embedded epitope imprinted polymer for in vivo targeted imaging of HeLa cells overexpressing EGFR.
    • 79. Riedl T, van Boxtel E, Bosch M, Parren PW, Gerritsen AF. High-throughput screening for internalizing antibodies by homogeneous fluorescence imaging of a pH-activated probe. J. Biomol. Screening 21(1), 12–23 (2016).
    • 80. Dong W, Zhou SQ, Dong Y, Wang JW, Ge X, Sui LL. The preparation of ethylenediamine-modified fluorescent carbon dots and their use in imaging of cells. Luminescence 30(6), 867–871 (2015).
    • 81. Hamd-Ghadareh S, Salimi A, Parsa S, Fathi F. Simultaneous biosensing of CA125 and CA15-3 tumor markers and imaging of OVCAR-3 and MCF-7 cells lines via bi-color FRET phenomenon using dual blue-green luminescent carbon dots with single excitation wavelength. Int. J. Biol. Macromol. 118(Pt A), 617–628 (2018).
    • 82. Han C, Xu H, Wang R et al. Synthesis of a multifunctional manganese(II)–carbon dots hybrid and its application as an efficient magnetic–fluorescent imaging probe for ovarian cancer cell imaging. J. Mater. Chem. B 4(35), 5798–5802 (2016).
    • 83. Lee CH, Rajendran R, Jeong MS et al. Bioimaging of targeting cancers using aptamer-conjugated carbon nanodots. Chem. Commun. (Camb). 49(58), 6543–6545 (2013).
    • 84. Tan MQ, Li XT, Wu H, Wang BB, Wu J. N-doped carbon dots derived from bovine serum albumin and formic acid with one- and two-photon fluorescence for live cell nuclear imaging. Colloids Surf. B Biointerfaces 136, 141–149 (2015).
    • 85. Yang YY, Wang XF, Liao GC et al. iRGD-decorated red shift emissive carbon nanodots for tumor targeting fluorescence imaging. J. Colloid. Interface Sci. 509, 515–521 (2018).
    • 86. Song GH, Meng FS, Li DF et al. Influence of cancer screening in a large population on the trends of cancer incidence. J. Mod. Oncol. 20(8), 1711–1713 (2012).
    • 87. Cantisani V, David E, Sidhu PS et al. Parotid Gland Lesions: Multiparametric Ultrasound and MRI Features. Ultraschall Medizin 37(5), 454–471 (2016).
    • 88. Michielsen K, Dresen R, Vanslembrouck R et al. Diagnostic value of whole body diffusion-weighted MRI compared to computed tomography for pre-operative assessment of patients suspected for ovarian cancer. Eur. J. Cancer 83, 88–98 (2017).
    • 89. Tong GY, Yu ZQ, Ge CC. Application of coarse core biopsy guided by colour doppler ultrasound in diagnosis of parotid tumors. J. Oral Sci. Res. 33(3), 336–338 (2017).
    • 90. Chen C, Li JD, Huang H, Feng YL, Wang LH, Chen L. Diagnostic value of multiple tumor marker detection for mature and immature teratoma of the ovary. Chin. J. Cancer 27(1), 92–95 (2008).
    • 91. Zhou WN, Srichai MB. Multi-modality imaging assessment of pericardial masses. Cardiol. Rep. 19(4), 32 (2017).
    • 92. Wan JCM, Massie C, Garcia-Corbacho J et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer 17(4), 223–238 (2017).
    • 93. Yu W, Hurley J, Roberts D et al. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann. Oncol. 32(4), 466–477 (2021).
    • 94. Azizi M, Valizadeh H, Shahgolzari M et al. Synthesis of self-targeted carbon dot with ultrahigh quantum yield for detection and therapy of cancer. ACS Omega 5(38), 24628–24638 (2020).
    • 95. Lai YX, Wang LJ, Liu Y et al. Immunosensors based on nanomaterials for detection of tumor markers. J. Biomed. Nanotechnol. 14(1), 44–65 (2018).
    • 96. Sun S, Chen Q, Tang ZD et al. Tumor microenvironment stimuli-responsive fluorescence imaging and synergistic cancer therapy by carbon-dot-Cu2+ nanoassemblies. Angew. Chem. Int. Ed. Engl. 59(47), 21041–21048 (2020).
    • 97. Mordente A, Meucci E, Martorana GE, Silvestrini A. Cancer biomarkers discovery and validation: state of the art, problems and future perspectives. Adv. Exp. Med. Biol. 867, 9–26 (2015).
    • 98. Zheng M, Ruan SB, Liu S et al. Self-targeting fluorescent carbon dots for diagnosis of brain cancer cells. ACS Nano 9(11), 11455–11461 (2015).
    • 99. Zhang PS, Hou Y, Zeng JF et al. Coordinatively unsaturated Fe3+ based activatable probes for enhanced MRI and therapy of tumors. Angew. Chem. Int. Ed. Engl. 58(32), 11088–11096 (2019).
    • 100. Miao X, Yan XL, Qu D, Li DB, Tao FF, Sun ZC. Red emissive sulfur, nitrogen codoped carbon dots and their application in ion detection and theraonostics. ACS Appl. Mater. Interfaces 9(22), 18549–18556 (2017).
    • 101. Qi HJ, Teng M, Liu M et al. Biomass-derived nitrogen-doped carbon quantum dots: highly selective fluorescent probe for detecting Fe3+ ions and tetracyclines. J. Colloid. Interface Sci. 539, 332–341 (2019).
    • 102. Raj SK, Choudhary B, Yadav A, Patidar R, Mishra A, Kulshrestha V. Green-synthesized, pH-stable and biocompatible carbon nanosensor for Fe3+: an experimental and computational study. Heliyon 8(4), e09259 (2022).
    • 103. Zhong ZL, Li XY, Liu SY, Zhang CW, Xu XP, Liao LY. In vivo study of a novel, safe, rapid, and targeted red carbon dot probe for recognition of tumors with high expression of folate enzyme. RSC Adv. 11(46), 28809–28817 (2021).
    • 104. Krebs MG, Hou JM, Ward TH, Blackhall FH, Dive C. Circulating tumour cells: their utility in cancer management and predicting outcomes. Ther. Adv. Med. Oncol. 2(6), 351–365 (2010).
    • 105. Liu PF, Wang L, Zhao KR et al. High luminous efficiency Au@CDs for sensitive and label-free electrochemiluminescent detection of circulating tumor cells in serum. Sens. Actuators B 316, 128131 (2020).
    • 106. Kong TT, Zhou RH, Zhang YJ, Hao LY, Cai XX, Zhu BF. AS1411 aptamer modified carbon dots via polyethylenimine-assisted strategy for efficient targeted cancer cell imaging. Cell Prolif. 53(1), e12713 (2020).
    • 107. Baryeh K, Takalkar S, Lund M, Liu G. Development of quantitative immunochromatographic assay for rapid and sensitive detection of carbohydrate antigen 19-9 (CA 19-9) in human plasma. J. Pharm. Biomed. Anal. 146, 285–291 (2017).
    • 108. Alarfaj NA, El-Tohamy MF, Oraby HF. CA 19-9 pancreatic tumor marker fluorescence immunosensing detection via immobilized carbon quantum dots conjugated gold nanocomposite. Int. J. Mol. Sci. 19(4), 1162 (2018).
    • 109. Tang ZX, Ma ZF. Multiple functional strategies for amplifying sensitivity of amperometric immunoassay for tumor markers: a review. Biosens. Bioelectron. 98, 100–112 (2017).
    • 110. Xu LL, Zhang W, Shang L et al. Perylenetetracarboxylic acid and carbon quantum dots assembled synergistic electrochemiluminescence nanomaterial for ultra-sensitive carcinoembryonic antigen detection. Biosens. Bioelectron. 103, 6–11 (2018).
    • 111. Khan KM, Rahim F, Halim SA et al. Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking. Bioorg. Med. Chem. 19(14), 4286–4294 (2011).
    • 112. Chang HC, Ho JA. Gold nanocluster-assisted fluorescent detection for hydrogen peroxide and cholesterol based on the inner filter effect of gold nanoparticles. Anal. Chem. 87(20), 10362–10367 (2015).
    • 113. Wu M, Sun LJ, Miao K, Wu Y, Fan LJ. Detection of Sudan dyes based on inner-filter effect with reusable conjugated polymer fibrous membranes. ACS Appl. Mater. Interfaces 10(9), 8287–8295 (2018).
    • 114. Gong PW, Sun L, Wang F et al. Highly fluorescent N-doped carbon dots with two-photon emission for ultrasensitive detection of tumor marker and visual monitor anticancer drug loading and delivery. Chem. Eng. J. 356, 995–1002 (2018).
    • 115. Markman M. The role of CA-125 in the management of ovarian cancer. Oncologist 2(1), 6–9 (1997).
    • 116. Omer WE, Abdelbar MF, El-Kemary NM, Fukata N, El-Kemary MA. Cancer antigen 125 assessment using carbon quantum dots for optical biosensing for the early diagnosis of ovarian cancer. RSC Adv. 11(49), 31047–31057 (2021).
    • 117. Ghirardello M, Shyam R, Liu X et al. Carbon dot-based fluorescent antibody nanoprobes as brain tumour glioblastoma diagnostics. Nanoscale Adv. 4(7), 1770–1778 (2022). • A recent study of carbon dots for the early diagnosis of glioblastoma.
    • 118. Chen ZY, Liao T, Wan LH et al. Dual-stimuli responsive near-infrared emissive carbon dots/hollow mesoporous silica-based integrated theranostics platform for real-time visualized drug delivery. Nano Res. 14(11), 4264–4273 (2021).
    • 119. Cho K, Wang X, Nie S, Chen ZG, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 14(5), 1310–1316 (2008).
    • 120. Kakran M, Li L. Carbon nanomaterials for drug delivery. Key Eng. Mater. 508, 76–80 (2012).
    • 121. Li Z, Tan SR, Li S, Shen Q, Wang KH. Cancer drug delivery in the nano era: an overview and perspectives (review). Oncol. Rep. 38(2), 611–624 (2017).
    • 122. Labatut AE, Mattheolabakis G. Non-viral based miR delivery and recent developments. Eur. J. Pharm. Biopharm. 128, 82–90 (2018).
    • 123. Manzano M, Vallet-Regí M. New developments in ordered mesoporous materials for drug delivery. J. Mater. Chem. 20(27), 5593–5604 (2010).
    • 124. Liu JJ, Li R, Yang B. Carbon dots: a new type of carbon-based nanomaterial with wide applications. ACS Cent. Sci. 6(12), 2179–2195 (2020).
    • 125. Kong TT, Hao LY, Wei YY, Cai XX, Zhu BF. Doxorubicin conjugated carbon dots as a drug delivery system for human breast cancer therapy. Cell Prolif. 51(5), e12488 (2018).
    • 126. D'souza S, Shankaran S, Koduru J, Kailasa S. Synthesis of fluorescent carbon dots using Daucus carota subsp. sativus roots for mitomycin drug delivery. Optik 158, 893–900 (2018).
    • 127. Zhang BY, Duan QQ, Li Y, Wang JM, Zhang WD, Sang SB. pH and redox dual-sensitive drug delivery system constructed based on fluorescent carbon dots. RSC Adv. 11(5), 2656–2663 (2021). •• An interesting study of carbon dots with the dual-responsive pH and redox drug-delivery system.
    • 128. D'souza S, Deshmukh B, Bhamore J, Rawat K, Lenka N, Kailasa S. Synthesis of fluorescent nitrogen-doped carbon dots from dried shrimps for cell imaging and boldine drug delivery system. RSC Adv. 6, 12169–12179 (2016).
    • 129. Zheng M, Liu S, Li J et al. Integrating oxaliplatin with highly luminescent carbon dots: an unprecedented theranostic agent for personalized medicine. Adv. Mater. 26(21), 3554–3560 (2014).
    • 130. Yang L, Wang ZR, Wang J et al. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy. Nanoscale 8(12), 6801–6809 (2016).
    • 131. Zeng QH, Shao D, He X et al. Carbon dots as a trackable drug delivery carrier for localized cancer therapy in vivo. J. Mater. Chem. B 4(30), 5119–5126 (2016).
    • 132. Yuan YF, Guo B, Hao LY et al. Doxorubicin-loaded environmentally friendly carbon dots as a novel drug delivery system for nucleus targeted cancer therapy. Colloids Surf. B Biointerfaces 159, 349–359 (2017).
    • 133. Zhang M, Zhou NL, Yuan P, Su YT, Shao MN, Chi C. Graphene oxide and adenosine triphosphate as a source for functionalized carbon dots with applications in pH-triggered drug delivery and cell imaging. RSC Adv. 7(15), 9284–9293 (2017).
    • 134. Duan QQ, Ma Y, Che MX et al. Fluorescent carbon dots as carriers for intracellular doxorubicin delivery and track. J. Drug Deliv. Sci. Technol. 49, 527–533 (2018).
    • 135. Sun YQ, Zheng SH, Liu L et al. The cost-effective preparation of green fluorescent carbon dots for bioimaging and enhanced intracellular drug delivery. Nanoscale Res. Lett. 15(1), 55 (2020).
    • 136. Horo H, Saha M, Das H, Mandal B, Kundu LM. Synthesis of highly fluorescent, amine-functionalized carbon dots from biotin-modified chitosan and silk-fibroin blend for target-specific delivery of antitumor agents. Carbohydr. Polym. 277, 118862 (2022). • A meaningful study of carbon dots with target specificity in cancer cells.
    • 137. Chandrasekaran P, Sivaraman G, Rasala S, Sethuraman MG, Kotla NG, Rochev Y. Quercetin conjugated fluorescent nitrogen-doped carbon dots for targeted cancer therapy application. Soft Matter 18(30), 5645–5653 (2022).
    • 138. Li SH, Amat D, Peng ZL et al. Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells. Nanoscale 8(37), 16662–16669 (2016).
    • 139. Gao N, Yang W, Nie HL et al. Turn-on theranostic fluorescent nanoprobe by electrostatic self-assembly of carbon dots with doxorubicin for targeted cancer cell imaging, in vivo hyaluronidase analysis, and targeted drug delivery. Biosens. Bioelectron. 96, 300–307 (2017).
    • 140. Pooresmaeil M, Namazi H. Folic acid-modified photoluminescent dialdehyde carboxymethyl cellulose crosslinked bionanogels for pH-controlled and tumor-targeted co-drug delivery. Int. J. Biol. Macromol. 200, 247–262 (2022).
    • 141. Zanetto A, Campello E, Spiezia L, Burra P, Simioni P, Russo FP. Cancer-associated thrombosis in cirrhotic patients with hepatocellular carcinoma. Cancers (Basel) 10(11), 450 (2018).
    • 142. Zhang M, Yuan P, Zhou NL, Su YT, Shao MN, Chi C. pH-Sensitive N-doped carbon dots–heparin and doxorubicin drug delivery system: preparation and anticancer research. RSC Adv. 7(15), 9347–9356 (2017).
    • 143. Duan QQ, Ma L, Zhang BY et al. Construction and application of targeted drug delivery system based on hyaluronic acid and heparin functionalised carbon dots. Colloids Surf. B Biointerfaces 188, 110768 (2020).
    • 144. Hettiarachchi SD, Graham RM, Mintz KJ et al. Triple conjugated carbon dots as a nano-drug delivery model for glioblastoma brain tumors. Nanoscale 11(13), 6192–6205 (2019).
    • 145. Yu HL, Lv XF, Wu LL et al. Doxorubicin-loaded fluorescent carbon dots with PEI passivation as a drug delivery system for cancer therapy. Nanoscale 12(33), 17222–17237 (2020).
    • 146. Tao F, Ai XZ, Ong HM, Zhao YL. Dual-responsive carbon dots for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. ACS Appl. Mater. Interfaces 8(29), 18732–18740 (2016).
    • 147. Shu Y, Lu J, Mao QX et al. Ionic liquid mediated organophilic carbon dots for drug delivery and bioimaging. Carbon 114, 324–333 (2017).
    • 148. Mehta VN, Chettiar SS, Bhamore JR, Kailasa SK, Patel RM. Green synthetic approach for synthesis of fluorescent carbon dots for lisinopril drug delivery system and their confirmations in the cells. J. Fluoresc. 27(1), 111–124 (2017).
    • 149. Shao YY, Zhu CY, Fu ZF et al. Green synthesis of multifunctional fluorescent carbon dots from mulberry leaves (Morus alba L.) residues for simultaneous intracellular imaging and drug delivery. J. Nanopart. Res. 22(8), 229 (2020).
    • 150. Ghosal K, Ghosh A. Carbon dots: the next generation platform for biomedical applications. Mater. Sci. Eng. C Mater. Biol. Appl. 96, 887–903 (2019).
    • 151. Li H, Yan X, Kong D et al. Recent advances in carbon dots for bioimaging applications. Nanoscale Horiz. 5(2), 218–234 (2020).
    • 152. Tian XT, Yin XB. Carbon dots, unconventional preparation strategies, and applications beyond photoluminescence. Small 15(48), e1901803 (2019).
    • 153. Ansari L, Hallaj S, Hallaj T, Amjadi M. Doped-carbon dots: recent advances in their biosensing, bioimaging and therapy applications. Colloids Surf. B Biointerfaces 203, 111743 (2021).
    • 154. Sri S, Kumar R, Panda AK, Solanki PR. Highly biocompatible, fluorescence, and zwitterionic carbon dots as a novel approach for bioimaging applications in cancerous cells. ACS Appl. Mater. Interfaces 10(44), 37835–37845 (2018).
    • 155. Hong H, Baatar D, Hwang SG. Anticancer activities of ginsenosides, the main active components of ginseng. Evid. Based Complement. Alternat. Med. 2021, 8858006 (2021).
    • 156. Yao H, Li J, Song YB et al. Synthesis of ginsenoside Re-based carbon dots applied for bioimaging and effective inhibition of cancer cells. Int. J. Nanomed. 13, 6249–6264 (2018).
    • 157. Lu ST, Liu LP, Wang HN et al. Synthesis of dual functional gallic-acid-based carbon dots for bioimaging and antitumor therapy. Biomater. Sci. 7(8), 3258–3265 (2019).
    • 158. Li YC, Wang Y, Li DD, Zhang Y, Zhao TC, Li CF. Procaine is a specific DNA methylation inhibitor with anti-tumor effect for human gastric cancer. J. Cell. Biochem. 119(2), 2440–2449 (2018).
    • 159. Li C, Gao SH, Li XP, Li C, Ma LJ. Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA. Oncol. Res. 26(2), 209–217 (2018).
    • 160. Zhao XM, Qi TY, Yang MX et al. Synthesis of dual functional procaine-derived carbon dots for bioimaging and anticancer therapy. Nanomedicine (Lond.) 15(7), 677–689 (2020).
    • 161. Bajpai VK, Khan I, Shukla S et al. Multifunctional N-P-doped carbon dots for regulation of apoptosis and autophagy in B16F10 melanoma cancer cells and in vitro imaging applications. Theranostics 10(17), 7841–7856 (2020).
    • 162. Wang Y, Huo TT, Jiang HL et al. Sugar-originated carbon nanodots selectively damage the tumor and enhance the sensitivity of chemotherapy. Nano Today 38, 101200 (2021).
    • 163. Yao L, Zhao MM, Luo QW et al. Carbon quantum dots-based nanozyme from coffee induces cancer cell ferroptosis to activate antitumor immunity. ACS Nano. 16(6), 9228–9239 (2022). •• A recent study of nanozyme-like carbon dots promoting iron death in cancer cells.
    • 164. Liu X, Liu YL, Thakor AS et al. Endogenous NO-releasing carbon nanodots for tumor-specific gas therapy. Acta Biomater. 136, 485–494 (2021). •• An interesting study of carbon dots reducing multidrug-resistant responses in cancer chemotherapy.
    • 165. Simsek S, Sukuroglu AA, Yetkin D, Ozbek B, Battal D, Genc R. DNA-damage and cell cycle arrest initiated anti-cancer potency of super tiny carbon dots on MCF7 cell line. Sci. Rep. 10(1), 13880 (2020).
    • 166. Li CW, Cheng Y, Li DW et al. Antitumor applications of photothermal agents and photothermal synergistic therapies. Int. J. Mol. Sci. 23(14), 7909 (2022).
    • 167. Kadkhoda J, Tarighatnia A, Barar J, Aghanejad A, Davaran S. Recent advances and trends in nanoparticles based photothermal and photodynamic therapy. Photodiagn. Photodyn. Ther. 37, 102697 (2022).
    • 168. Lagos KJ, Buzza HH, Bagnato VS, Romero MP. Carbon-based materials in photodynamic and photothermal therapies applied to tumor destruction. Int. J. Mol. Sci. 23(1), 22 (2021).
    • 169. Zhong YT, Cen Y, Xu L, Li SY, Cheng H. Recent progress in carrier-free nanomedicine for tumor phototherapy. Adv. Healthcare Mater. 12(4), e2202307 (2023).
    • 170. Li SH, Zhou SX, Li YC et al. Exceptionally high payload of the IR780 iodide on folic acid-functionalized graphene quantum dots for targeted photothermal therapy. ACS Appl. Mater. Interfaces 9(27), 22332–22341 (2017).
    • 171. Choi CA, Lee JE, Mazrad ZAI et al. Dual-responsive carbon dot for pH/redox-triggered fluorescence imaging with controllable photothermal ablation therapy of cancer. ChemMedChem 13(14), 1459–1468 (2018).
    • 172. Peng XY, Wang R, Wang TJ et al. Carbon dots/Prussian blue satellite/core nanocomposites for optical imaging and photothermal therapy. ACS Appl. Mater. Interfaces 10(1), 1084–1092 (2018).
    • 173. Bai YT, Zhang B, Chen L et al. Facile one-pot synthesis of polydopamine carbon dots for photothermal therapy. Nanoscale Res. Lett. 13(1), 287 (2018).
    • 174. Liu HJ, Li CW, Qian Y et al. Magnetic-induced graphene quantum dots for imaging-guided photothermal therapy in the second near-infrared window. Biomaterials 232, 119700 (2020).
    • 175. Kim D, Jo G, Chae Y et al. Bioinspired Camellia japonica carbon dots with high near-infrared absorbance for efficient photothermal cancer therapy. Nanoscale 13(34), 14426–14434 (2021).
    • 176. Zhao SJ, Yan L, Cao MY et al. Near-infrared light-triggered lysosome-targetable carbon dots for photothermal therapy of cancer. ACS Appl. Mater. Interfaces 13(45), 53610–53617 (2021).
    • 177. Choi SY, Baek SH, Chang SJ et al. Synthesis of upconversion nanoparticles conjugated with graphene oxide quantum dots and their use against cancer cell imaging and photodynamic therapy. Biosens. Bioelectron. 93, 267–273 (2017).
    • 178. Yang D, Yang GX, Gai SL, He F, Li CX, Yang PP. Multifunctional theranostics for dual-modal photodynamic synergistic therapy via stepwise water splitting. ACS Appl. Mater. Interfaces 9(8), 6829–6838 (2017).
    • 179. Wang Z, Zhang L, Zhang K et al. Application of carbon dots and their composite materials for the detection and removal of radioactive ions: a review. Chemosphere 287(Pt 3), 132313 (2022).
    • 180. Lesani P, Singh G, Viray C et al. Two-photon dual-emissive carbon dot-based probe: deep-tissue imaging and ultrasensitive sensing of intracellular ferric ions. ACS Appl. Mater. Interfaces 12(16), 18395–18406 (2020).
    • 181. Nair A, Haponiuk JT, Thomas S, Gopi S. Natural carbon-based quantum dots and their applications in drug delivery: a review. Biomed. Pharmacother. 132, 110834 (2020).
    • 182. Wang XD, Yang XH, Zhang C et al. Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy. Proc. Natl Acad. Sci. USA 117(12), 6640–6650 (2020).
    • 183. Meng WF, Xue SH, Chen Y. The role of CXCL12 in tumor microenvironment. Gene 641, 105–110 (2018).