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image of Nano-formulated Flavonoids in Cancer Prevention and Treatment: A Systematic Review of Therapeutic Potential

Abstract

Introduction

Medical research has confirmed that cancer is the second leading cause of death due to illness and a significant public health issue. Reports indicate that lung cancer is most commonly diagnosed in older males aged 60 to 84. Interestingly, females under the age of 45 exhibit a higher incidence rate of lung cancer compared to males. The use of conventional drugs triggers the activation of nuclear factor kappa B (NF-κB) in tumor cells, which leads to reduced cell death and increased drug resistance. Additionally, this activation causes toxicity, resulting in a poor therapeutic response. The objective of this review is to focus on the anticancer potential of various flavonoids and their nanoformulations, which can be integrated into the treatment of cancer.

Methods

The screening process involved collecting the required data, including the global status of cancer, its prevalence, conventional therapies for cancer, the challenges and limitations of traditional treatments, the current search for phytomedicines as alternative therapy, the role of flavonoids in chemotherapy, and the development of advanced nano-delivery systems of flavonoids for cancer treatment.

Results

Selected polyphenolic and flavonoid compounds such as quercetin, naringenin, luteolin, genistein, curcumin, epigallocatechin gallate, fisetin, rutin, myricetin, apigenin, and hesperidin possess protective abilities and are responsible for minimizing the chances of tumor formation through NF-κB and cytokine modulation, as studied by both and methods. They can disrupt the function of several growth factors and transcription factors that support tumor growth, including VEGF, AP-1, and the NF-κB pathway. According to and research, many nanotechnology-based strategies have been developed to transport flavonoids to cancer cells to overcome these limitations. However, the therapeutic properties of flavonoids are hampered by poor systemic bioavailability.

Discussion

Here, we highlight the importance of flavonoid formulations based on nanoparticles for the safe delivery of flavonoids to tumor tissues with high efficiency by modulating key signaling pathways and influencing the tumor microenvironment.

Conclusion

The applications of nanotechnology for enhancing the bioavailability and targeting of flavonoids in cancer therapy have been explored. This review emphasizes the anticancer potential of various flavonoids and their nanoformulations, which can be integrated into the treatment of cancer.

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2026-01-22
2026-03-10
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References

  1. Hazafa A. Rehman K.U. Jahan N. Jabeen Z. The role of polyphenol (Flavonoids) compounds in the treatment of cancer cells. Nutr. Cancer 2020 72 3 386 397 10.1080/01635581.2019.1637006 31287738
    [Google Scholar]
  2. Sangamithra A. The causes of cancer: An analysis of avoidable risk factors. Shanlax Int J Econ 2021 9 2 37 40 10.34293/economics.v9i2.3727
    [Google Scholar]
  3. Watkins E.J. Overview of breast cancer. JAAPA 2019 32 10 13 17 10.1097/01.JAA.0000580524.95733.3d 31513033
    [Google Scholar]
  4. Ferlay J. Soerjomataram I. Dikshit R. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015 136 5 E359 E386 10.1002/ijc.29210 25220842
    [Google Scholar]
  5. Guo L. Zhu C. Cai L. Global burden of lung cancer in 2022 and projected burden in 2050. Chin. Med. J. (Engl.) 2024 137 21 2577 2582 10.1097/CM9.0000000000003268 39313774
    [Google Scholar]
  6. Alaryani F.S. Turki Alrdahe S.S. A review of treatment, risk factors, and incidence of colorectal cancer. Int J Appl Pharm 2022 14 1 1 6 10.22159/ijap.2022v14i1.42820
    [Google Scholar]
  7. Ng C.J. Teo C.H. Abdullah N. Tan W.P. Tan H.M. Relationships between cancer pattern, country income and geographical region in Asia. BMC Cancer 2015 15 1 613 10.1186/s12885‑015‑1615‑0 26335225
    [Google Scholar]
  8. Gyanani V. Haley J.C. Goswami R. Challenges of current anticancer treatment approaches with focus on liposomal drug delivery systems. Pharmaceuticals 2021 14 9 835 10.3390/ph14090835 34577537
    [Google Scholar]
  9. Nonnekens J. Hoeijmakers J.H.J. After surviving cancer, what about late life effects of the cure? EMBO Mol. Med. 2017 9 1 4 6 10.15252/emmm.201607062 27852619
    [Google Scholar]
  10. Talib W.H. Awajan D. Hamed R.A. Azzam A.O. Mahmod A.I. AL-Yasari IH. Combination anticancer therapies using selected phytochemicals. Molecules 2022 27 17 5452 10.3390/molecules27175452 36080219
    [Google Scholar]
  11. Hashim G.M. Shahgolzari M. Hefferon K. Yavari A. Venkataraman S. Plant-derived anti-cancer therapeutics and biopharmaceuticals. Bioengineering 2024 12 1 7 10.3390/bioengineering12010007 39851281
    [Google Scholar]
  12. Sharma V. Chaudhary A.A. Bawari S. Unraveling cancer progression pathways and phytochemical therapeutic strategies for its management. Front. Pharmacol. 2024 15 1414790 10.3389/fphar.2024.1414790 39246660
    [Google Scholar]
  13. Dini I. Grumetto L. Recent advances in natural polyphenol research. Molecules 2022 27 24 8777 10.3390/molecules27248777 36557912
    [Google Scholar]
  14. Abhinav S. Pentu N. Rao T.R. An updated review on flavonoids. The Pharma Innov J 2024 13 2 1 8 10.22271/tpi.2024.v13.i2a.25347
    [Google Scholar]
  15. Panchal N.B. Vaghela V.M. Diet-derived flavonoids: Bridging epidemiological chemoprevention and preclinical anti-tumor mechanisms in clinical oncology. J. Nat. Rem. 2024 24 8 1633 1651 10.18311/jnr/2024/43883
    [Google Scholar]
  16. Chen S. Wang X. Cheng Y. Gao H. Chen X. A review of classification, biosynthesis, biological activities and potential applications of flavonoids. Molecules 2023 28 13 4982 10.3390/molecules28134982 37446644
    [Google Scholar]
  17. Jadhav M. Kale M. Rathod M. Kohale D. Novel drug delivery systems for delivery of herbal medicine. Int J Adv Res Sci Commun Technol 2023 302 314
    [Google Scholar]
  18. Aung T. Qu Z. Kortschak R. Adelson D. Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int. J. Mol. Sci. 2017 18 3 656 10.3390/ijms18030656 28304343
    [Google Scholar]
  19. Hasan-Abad A.M. Atapour A. Sobhani-Nasab A. Motedayyen H. ArefNezhad R. Plant‐based anticancer compounds with a focus on breast cancer. Cancer Rep. 2024 7 10 e70012 10.1002/cnr2.70012 39453820
    [Google Scholar]
  20. El Orfi N Boutayeb S Haddou Rahou B Errihani H. Use of medicinal plants by cancer patients under chemotherapy in the Northwest of Morocco (Rabat area): Cross-sectional study. J Evid Based Integr Med 2022 27 2515690X221128036 10.1177/2515690X221128036 36254459
    [Google Scholar]
  21. Kaur H. Plants as a source of anticancer agents. J Nat Prod Plant Resour 2011 1 119 124
    [Google Scholar]
  22. Mohire N.C. Jha S.K. Kumar R. Laware R.B. Natural products and their therapeutic advancement in management of cancer. Futuristic Trend Pharm Nurs 2024 3 172 184
    [Google Scholar]
  23. Anees N. Ghafoor N. Sattar Q. Siddiqa A. Khatoon A. Akbar A.L.I. Unveiling the defensive role of flavonoids: A toxicant countermeasure. Zoology: Advancements and Research Trends. India FahumSci 2024 124 131 10.61748/Zool.2024/16
    [Google Scholar]
  24. Tang S. Wang B. Liu X. Xi W. Yue Y. Tan X. Structural insights and biological activities of flavonoids: Implications for novel applications. Food Frontiers 2024 6 218 247 10.1002/fft2.494
    [Google Scholar]
  25. Kapare H.S. Patil N. Bhosale M. Kulkarni D. Bhole R. Nanocochleate-based delivery of quercetin with enhanced therapeutic potential: Formulation, cytotoxicity and pharmacokinetics study. Future J. Pharm. Sci. 2024 10 1 1 13 10.1186/s43094‑024‑00732‑z
    [Google Scholar]
  26. Yadav N. Tripathi A. Parveen A. Parveen S. Banerjee M. PLGA-quercetin nano-formulation inhibits cancer progression via mitochondrial dependent caspase-3,7 and independent FoxO1 activation with concomitant PI3K/AKT suppression. Pharmaceutics 2022 14 7 1326 10.3390/pharmaceutics14071326 35890222
    [Google Scholar]
  27. Keshavarz F. Dorfaki M. Bardania H. Khosravani F. Nazari P. Ghalamfarsa G. Quercetin-loaded liposomes effectively induced apoptosis and decreased the epidermal growth factor receptor expression in colorectal cancer cells: An in vitro study. Iran. J. Med. Sci. 2023 48 3 321 328 10.30476/IJMS.2022.95272.2658 37791331
    [Google Scholar]
  28. Samantaray A. Pradhan D. Nayak N.R. Nanoquercetin based nanoformulations for triple negative breast cancer therapy and its role in overcoming drug resistance. Discov. Oncol. 2024 15 1 452 10.1007/s12672‑024‑01239‑y 39287822
    [Google Scholar]
  29. Vahedian Sadeghi R. Parsania M. Sadeghizadeh M. Haghighat S. Investigation of curcumin-loaded OA400 nanoparticle’s effect on the expression of E6 and E7 human papilloma-virus oncogenes and P53 and Rb factors in HeLa cell line. Iran. J. Pharm. Res. 2022 21 1 e130762 10.5812/ijpr‑130762 36710992
    [Google Scholar]
  30. Minafra L. Porcino N. Bravatà V. Radiosensitizing effect of curcumin-loaded lipid nanoparticles in breast cancer cells. Sci. Rep. 2019 9 1 11134 10.1038/s41598‑019‑47553‑2 31366901
    [Google Scholar]
  31. Karami P. Othman G. Housein Z. Nanoformulation of polyphenol curcumin enhances cisplatin-induced apoptosis in drug-resistant MDA-MB-231 breast cancer cells. Molecules 2022 27 9 2917 10.3390/molecules27092917 35566271
    [Google Scholar]
  32. Harakeh S. Saber S.H. Al-Raddadi R. Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells. Artif. Cells Nanomed. Biotechnol. 2023 51 1 361 370 10.1080/21691401.2023.2238756 37524306
    [Google Scholar]
  33. Mod Razif MRF Chan SY Chew Y-L Hassan M Ahmad Hisham S Abdul Rahman S Recent developments in luteolin loaded nanoformulations for enhanced anti carcinogenic activities: Insights from in vitro and in vivo studies. Sci 2024 6 4 10.3390/sci6040068
    [Google Scholar]
  34. Zheng S. Cheng Y. Teng Y. Application of luteolin nanomicelles anti-glioma effect with improvement in vitro and in vivo. Oncotarget 2017 8 37 61146 61162 10.18632/oncotarget.18019 28977853
    [Google Scholar]
  35. Majumdar D. Jung K.H. Zhang H. Luteolin nanoparticle in chemoprevention: In vitro and in vivo anticancer activity. Cancer Prev. Res. 2014 7 1 65 73 10.1158/1940‑6207.CAPR‑13‑0230 24403290
    [Google Scholar]
  36. Yan H. Wei P. Song J. Jia X. Zhang Z. Enhanced anticancer activity in vitro and in vivo of luteolin incorporated into long-circulating micelles based on DSPE-PEG2000 and TPGS. J. Pharm. Pharmacol. 2016 68 10 1290 1298 10.1111/jphp.12598 27465923
    [Google Scholar]
  37. Zadeh Z.K. Arab S. Kazemi S. Arabhalvaee M. Afraz E.S. Bahraminasab M. Anticancer effect of Epigallocatechin Gallate Loaded Nanoparticles on Head and Neck Cancer. Research square 2024 10.21203/rs.3.rs‑3849470/v1
    [Google Scholar]
  38. Baranei M. Taheri R.A. Tirgar M. Anticancer effect of green tea extract (GTE)-Loaded pH-responsive niosome Coated with PEG against different cell lines. Mater. Today Commun. 2021 26 101751 10.1016/j.mtcomm.2020.101751
    [Google Scholar]
  39. Chen B.H. Hsieh C.H. Tsai S.Y. Wang C.Y. Wang C.C. Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway. Sci. Rep. 2020 10 1 5163 10.1038/s41598‑020‑62136‑2 32198390
    [Google Scholar]
  40. Elsori D. Pandey P. Ramniwas S. Naringenin as potent anticancer phytocompound in breast carcinoma: From mechanistic approach to nanoformulations based therapeutics. Front. Pharmacol. 2024 15 1406619 10.3389/fphar.2024.1406619 38957397
    [Google Scholar]
  41. Bhia M. Motallebi M. Abadi B. Naringenin nano-delivery systems and their therapeutic applications. Pharmaceutics 2021 13 2 291 10.3390/pharmaceutics13020291 33672366
    [Google Scholar]
  42. Dewangan H.K. Maurya L. Sharma R. Shah K. Soni S. Singh S. Optimization, evaluation and delivery of genistein loaded long circulating nanostructured lipid carriers for treatment of cancer melanoma cells. Preprint 2022 10.21203/rs.3.rs‑2042700/v1
    [Google Scholar]
  43. Pool H. Campos-Vega R. Herrera-Hernández M.G. Development of genistein-PEGylated silica hybrid nanomaterials with enhanced antioxidant and antiproliferative properties on HT29 human colon cancer cells. Am. J. Transl. Res. 2018 10 8 2306 2323 30210672
    [Google Scholar]
  44. Iqbal FM Rodríguez-Nogales C Boulens N Delie F Formulation and optimization of transferrin-modified genistein nanocrystals: In vitro anti-cancer assessment and pharmacokinetic evaluation. Int J Pharm 2024 667 Pt A 124863 10.1016/j.ijpharm.2024.124863 39447935
    [Google Scholar]
  45. Gao R. Lin P. Yang W. Bio-inspired nanodelivery platform: Platelet membrane-cloaked genistein nanosystem for targeted lung cancer therapy. Int. J. Nanomedicine 2024 19 10455 10478 10.2147/IJN.S479438 39430311
    [Google Scholar]
  46. Lagoa R. Graziani I. Lopez-Sanchez C. Garcia-Martinez V. Gutierrez-Merino C. Complex I and cytochrome c are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria. Biochim. Biophys. Acta Bioenerg. 2011 1807 12 1562 1572 10.1016/j.bbabio.2011.09.022 22015496
    [Google Scholar]
  47. Gossner G. Choi M. Tan L. Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells. Gynecol. Oncol. 2007 105 1 23 30 10.1016/j.ygyno.2006.11.009 17234261
    [Google Scholar]
  48. Aboushanab A.R. El-Moslemany R.M. El-Kamel A.H. Mehanna R.A. Bakr B.A. Ashour A.A. Targeted fisetin-encapsulated β-cyclodextrin nanosponges for breast cancer. Pharmaceutics 2023 15 5 1480 10.3390/pharmaceutics15051480 37242722
    [Google Scholar]
  49. Cutone A. Rosa L. Ianiro G. Lactoferrin’s anti-cancer properties: Safety, selectivity, and wide range of action. Biomolecules 2020 10 3 456 10.3390/biom10030456 32183434
    [Google Scholar]
  50. Kharouba M. El-Kamel A. Mehanna R. Thabet E. Heikal L. Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: A repurposing approach. Drug Deliv. 2022 29 1 2925 2944 10.1080/10717544.2022.2120925 36081339
    [Google Scholar]
  51. Halder A. Jethwa M. Mukherjee P. Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells. Artif. Cells Nanomed. Biotechnol. 2020 48 1 1362 1371 10.1080/21691401.2020.1850465 33284038
    [Google Scholar]
  52. Ibrahim R. Kasabri V. Sunoqrot S. Shalabi D. Alkhateeb R. Alhiari Y. Preparation and characterization of rutin-encapsulated polymeric micelles and studies of synergism with bioactive benzoic acids and triazolofluoroquinolones as anticancer nanomedicines. Asian Pac. J. Cancer Prev. 2023 24 3 977 989 10.31557/APJCP.2023.24.3.977 36974553
    [Google Scholar]
  53. Ragab E.M. El Gamal D.M. Mohamed T.M. Khamis A.A. Therapeutic potential of chrysin nanoparticle-mediation inhibition of succinate dehydrogenase and ubiquinone oxidoreductase in pancreatic and lung adenocarcinoma. Eur. J. Med. Res. 2022 27 1 172 10.1186/s40001‑022‑00803‑y 36076266
    [Google Scholar]
  54. Jangid A.K. Solanki R. Patel S. Medicherla K. Pooja D. Kulhari H. Improving anticancer activity of chrysin using tumor microenvironment ph-responsive and self-assembled nanoparticles. ACS Omega 2022 7 18 15919 15928 10.1021/acsomega.2c01041 35571829
    [Google Scholar]
  55. Bonilla-Vidal L. Świtalska M. Espina M. Dually active apigenin-loaded nanostructured lipid carriers for cancer treatment. Int. J. Nanomedicine 2023 18 6979 6997 10.2147/IJN.S429565 38026534
    [Google Scholar]
  56. Mujtaba M.A. Alotaibi N.M. Alshehri S.M. Novel therapeutic approach in PEGylated chitosan nanoparticles of apigenin for the treatment of cancer via oral nanomedicine. Polymers 2022 14 20 4344 10.3390/polym14204344 36297920
    [Google Scholar]
  57. Wang W. Li Y. Wang H. Zhao X. The preparation of apigenin nanoparticles and the study of their anti-inflammatory and anti-tumor activities in vitro. Separations 2022 10 1 16 10.3390/separations10010016
    [Google Scholar]
  58. Bansal K. Bhati H. Vanshita, Bajpai M. New insights into therapeutic applications and nanoformulation approaches of hesperidin: An updated review. Pharmacol. Res. Mod. Chin. Med. 2024 10 100363 10.1016/j.prmcm.2024.100363
    [Google Scholar]
  59. Saad S. Ahmad I. Kawish S.M. Improved cardioprotective effects of hesperidin solid lipid nanoparticles prepared by supercritical antisolvent technology. Colloids Surf. B Biointerfaces 2020 187 110628 10.1016/j.colsurfb.2019.110628 31753617
    [Google Scholar]
  60. Gupta P. Sheikh A. Abourehab M.A.S. Kesharwani P. Amelioration of full-thickness wound using hesperidin loaded dendrimer-based hydrogel bandages. Biosensors 2022 12 7 462 10.3390/bios12070462 35884268
    [Google Scholar]
  61. Bagher Z. Ehterami A. Safdel M.H. Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model. J. Drug Deliv. Sci. Technol. 2020 55 101379 10.1016/j.jddst.2019.101379
    [Google Scholar]
  62. Sulaiman G.M. Waheeb H.M. Jabir M.S. Khazaal S.H. Dewir Y.H. Naidoo Y. Hesperidin loaded on gold nanoparticles as a drug delivery system for a successful biocompatible, anti-cancer, anti-inflammatory and phagocytosis inducer model. Sci. Rep. 2020 10 1 9362 10.1038/s41598‑020‑66419‑6 32518242
    [Google Scholar]
  63. Yang Z. Yang H. Dong X. Pu M. Ji F. Hesperidin loaded Zn2+ @ SA/PCT nanocomposites inhibit the proliferation and induces the apoptosis in colon cancer cells (HCT116) through the enhancement of pro-apoptotic protein expressions. J. Photochem. Photobiol. B 2020 204 111767 10.1016/j.jphotobiol.2019.111767 32006893
    [Google Scholar]
  64. Kelte Filho I Machado CS Diedrich C Optimized chitosan-coated gliadin nanoparticles improved the hesperidin cytotoxicity over tumor cells. Braz Arch Biol Technol 2021 64 spe e21200795 10.1590/1678‑4324‑75years‑2021200795
    [Google Scholar]
  65. Balunas M.J. Kinghorn A.D. Drug discovery from medicinal plants. Life Sci. 2005 78 5 431 441 10.1016/j.lfs.2005.09.012 16198377
    [Google Scholar]
  66. Baz S.M. Abd El-Ghani S.F. Therapeutic effect of luteolin natural extract versus its nanoparticles on tongue squamous cell carcinoma cell line, NCT03288298 2017 Available from: https://clinicaltrials.gov/study/NCT03288298
  67. Hua S. de Matos M.B.C. Metselaar J.M. Storm G. Current trends and challenges in the clinical translation of nanoparticulate nanomedicines: Pathways for translational development and commercialization. Front. Pharmacol. 2018 9 790 10.3389/fphar.2018.00790 30065653
    [Google Scholar]
  68. Khan H. Ullah H. Martorell M. Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. Semin. Cancer Biol. 2021 69 200 211 10.1016/j.semcancer.2019.07.023
    [Google Scholar]
  69. Pandey P. Lakhanpal S. Mahmood D. An updated review summarizing the anticancer potential of flavonoids via targeting NF-kB pathway. Front. Pharmacol. 2025 15 1513422 10.3389/fphar.2024.1513422 39834817
    [Google Scholar]
  70. Krajka-Kuźniak V. Belka M. Papierska K. Targeting STAT3 and NF-κBsignaling pathways in cancer prevention and treatment: The role of chalcones. Cancers 2024 16 6 1092 10.3390/cancers16061092 38539427
    [Google Scholar]
  71. Liskova A. Samec M. Koklesova L. Flavonoids as an effective sensitizer for anti-cancer therapy: Insights into multi-faceted mechanisms and applicability towards individualized patient profiles. EPMA J. 2021 12 2 155 176 10.1007/s13167‑021‑00242‑5 34025826
    [Google Scholar]
  72. Diaz D. Care A. Sunna A. Bioengineering strategies for protein-based nanoparticles. Genes 2018 9 7 370 10.3390/genes9070370 30041491
    [Google Scholar]
  73. Guo S.B. Meng Y. Lin L. Artificial intelligence alphafold model for molecular biology and drug discovery: A machine-learning-driven informatics investigation. Mol. Cancer 2024 23 1 223 10.1186/s12943‑024‑02140‑6 39369244
    [Google Scholar]
  74. Bernatavicius A. Šícho M. Janssen A.P.A. Hassen A.K. Preuss M. van Westen G.J.P. AlphaFold meets de novo drug design: Leveraging structural protein information in multitarget molecular generative models. J. Chem. Inf. Model. 2024 64 21 8113 8122 10.1021/acs.jcim.4c00309 39475544
    [Google Scholar]
  75. Gupta J.K. Nagabhoosanam N. Curcumin nanostructured drug delivery induces the anticancer and anti-inflammatory activity in vitro and in vivo. J Angiotherapy 2024 8 1 6
    [Google Scholar]
  76. Cortes M. Sun X. Anusha A. AlphaFold 3 modeling of DNA nanomotifs: Is it reliable? Nanoscale Horiz. 2025 10 7 1428 1435 10.1039/D5NH00059A 40424014
    [Google Scholar]
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