Citation: Jie WEI, Qing ZHOU, Dandan DING, Xiang JING, Fei LI. Photothermal toxicity of Prussian blue nanoparticles to cervical cancer cells[J]. Chinese Journal of Inorganic Chemistry, ;2025, 41(11): 2345-2357. doi: 10.11862/CJIC.20240435 shu

Photothermal toxicity of Prussian blue nanoparticles to cervical cancer cells

Jie WEI ¹ ,
Qing ZHOU ¹ ,
Dandan DING ¹ ,
Xiang JING ¹ ,
Fei LI ^2,,

1.
Henan Vocational University of Science and Technology, Zhoukou, Henan 466001, China
2.
Henan Key Laboratory of Rare Earth Functional Materials, Henan International Joint Laboratory of Biomedical Nanomaterials, Zhoukou Normal University, Zhoukou, Henan 466001, China

Corresponding author: Fei LI, lifei@zknu.edu.cn
Received Date: 9 December 2024
Revised Date: 30 July 2025

Figures(10)

To investigate the photothermal toxicity of Prussian blue nanoparticles (PB NPs) on cervical cancer cells (HeLa cells) and their underlying mechanisms, uniformly sized and well-dispersed PB NPs were synthesized. Using HeLa cells as the experimental model, techniques such as MTT assay, confocal microscopy, and flow cytometry were employed to evaluate the effects of PB NPs on cell viability, membrane permeability, apoptosis, cell cycle arrest, and reactive oxygen species (ROS) generation. The MTT assay revealed that PB NPs inhibited HeLa cell proliferation in a concentration and laser power-dependent manner. At a mass concentration of 50 μg·mL^-1 and an 808 nm laser irradiation with a power density of 0.2 W·cm^-2, PB NPs reduced HeLa cell viability to 24.2%. Trypan blue staining and Calcein-AM/PI double-staining confocal microscopy demonstrated that the photothermal cytotoxicity of PB NPs primarily manifests as increased cell membrane permeability. Annexin V-FITC flow cytometry indicated that PB NPs induce apoptosis in HeLa cells. Furthermore, DCFH-DA fluorescence assays and flow cytometry showed that 20 μg·mL^-1 PB NPs under 808 nm laser irradiation (0.3 W·cm^-2) elevated intracellular ROS levels by 11.5-fold and induced cell cycle arrest at the G2/M phase. The above results suggest that the photothermal toxicity effect of PB NPs on HeLa cells is achieved by increasing cell membrane permeability, inducing cell cycle arrest, elevating ROS generation, and triggering apoptosis.
- Prussian blue,
- nanoparticles,
- photothermal toxicity
1. [1]
  BRAY F, LAVERSANNE M, SUNG H, Ferlay J, Siegel R L, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA‒Cancer J. Clin., 2024,74(3):229-263. doi: 10.3322/caac.21834
2. [2]
  DASH S R, KUNDU C N. Photothermal therapy: A new approach to eradicate cancer[J]. Curr. Nanosci., 2022,18(1):31-47. doi: 10.2174/1573413717666210301112058
3. [3]
  LI X S, LOVELL J F, YOON J. Clinical development and potential of photothermal and photodynamic therapies for cancer[J]. Nat. Rev. Clin. Oncol., 2020,17(11):657-674. doi: 10.1038/s41571-020-0410-2
4. [4]
  ZHU L J, XIONG J B, DU Z, MA R, ZHANG X L, NUERNISHA A. Application of near-infrared fluorescence-photothermal nanoparticles in photothermal therapy for cervical cancer[J]. Chinese Journal of Biomedical Engineering, 2024,43(4):499-507.
5. [5]
  GU Y L, ZHU J Y, XIONG J B, NUERNISHA A. Application of Prussian blue nanoparticles in biomedical diagnosis and therapy[J]. Chinese Journal of Medical Physics, 2023,40(9):1161-1166.
6. [6]
  GAO X R, WANG Q W, CHENG C, LIN S J, LIN T, TING LIN, LIU C, HAN X. The application of Prussian blue nanoparticles in tumor diagnosis and treatment[J]. Sensors, 2020,20(23):1-22. doi: 10.1109/JSEN.2020.3032359
7. [7]
  FU G L, LIU W, FENG S S, YUE X L. Prussian blue nanoparticles operate as a new generation of photothermal ablation agents for cancer therapy[J]. Chem. Commun., 2012,48(94)11567. doi: 10.1039/c2cc36456e
8. [8]
  ZHANG S P, CHENG Y X, REN L, WEN K, Lü X L, YE S F, ZHOU X. Synthesis and photothermal properties of morphology-controlled Prussian blue nanoparticles[J]. Chem. J. Chinese Universities, 2018,39(2):359-366.
9. [9]
  TANG K Y, LI X, HU Y L, ZHANG X N, NAN L, QIANG F, SHAO J J, LI S K, XIU W J, SONG Y N, YANG D L, ZHANG J J. Recent advances in Prussian blue-based photothermal therapy in cancer treatment[J]. Biomater. Sci., 2023,11(13):4411-4429. doi: 10.1039/D3BM00509G
10. [10]
  HUANG Y F, SEFAH K, BAMRUNGSAP S, CHANG H T, TAN W. Selective photothermal therapy for mixed cancer cells using aptamer-conjugated nanorods[J]. Langmuir, 2008,24(20):11860-11865. doi: 10.1021/la801969c
11. [11]
  LIU T, TIAN Y T, GAO K, HAN X W, MIN R A, ZHAO W J, YIN C X. A photothermal agent with high photothermal conversion efficiency and high stability for cancer therapy[J]. Chinese J. Inorg. Chem., 2024,40(8):1622-1632. doi: 10.11862/CJIC.20240107
12. [12]
  TIAN Q W, JIANG F R, ZOU R J, LIU Q, CHEN Z G, ZHU M F, YANG S P, WANG J L, WANG J H, HU J Q. Hydrophilic Cu₉S₅ nanocrystals: A photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo[J]. ACS Nano, 2011,5(12):9761-9771. doi: 10.1021/nn203293t
13. [13]
  KE H T, WANG J R, DAI Z F, JIN Y S, QU E Z, XING Z W, GUO C X, YUE X L, LIU J B. Gold-nanoshelled microcapsules: A theranostic agent for ultrasound contrast imaging and photothermal therapy[J]. Angew. Chem.‒Int. Edit., 2011,50(13):3017-3021. doi: 10.1002/anie.201008286
14. [14]
  ZHANG X M, LI J Y, MA B, LI B S, SHI L L, GAO S G. Photothermal therapy effect and mechanism of Prussian blue nanoparticles on esophageal squamous cell carcinoma[J]. Chinese Journal of Cancer Prevention and Treatment, 2025,32(14):850-861.
15. [15]
  ESTELRICH J, BUSQUETS M. Prussian Blue: A nanozyme with versatile catalytic properties[J]. Int. J. Mol. Sci., 2021,22(11)5993. doi: 10.3390/ijms22115993
16. [16]
  WANG Q, LIU X, SUN Y J, YANG C. Prussian blue-loaded CoOOH nanosheets for antioxidant activity detection[J]. Modern Chemical Industry, 2023,43(2):234-238.
17. [17]
  BEI Y, LI W J, LI M Y, SU M, ZHANG J, HUANG Y, ZHU Y Z, LI J L, WU Y. Prussian blue nanoparticles promote diabetic skin wound healing[J]. Chinese Journal of Tissue Engineering Research, 2024,28(10):1526-1532.
18. [18]
  YE J J, ZHANG W X, NI J C, HU S R. Detection of hydrogen peroxide and glutathione by Fe-Co Prussian blue colorimetric method[J]. Journal of Minnan Normal University (Natural Science Edition), 2024,37(2):52-63.
19. [19]
  ZENG X M, YAN S G, CHEN P, DU W, LIU B F. Modulation of tumor microenvironment by metal-organic-framework-derived nanoenzyme for enhancing nucleus-targeted photodynamic therapy[J]. Nano Res., 2020,13(6):1527-1535. doi: 10.1007/s12274-020-2746-4
20. [20]
  ZHAO Q, LIU Z. Research progress on tumor hypoxia regulation and radiotherapy enhancement based on nano-biomaterials[J]. Cancer Research on Prevention and Treatment, 2021,48(2):109-114.
21. [21]
  XIAO J J, LI Y, LIANG J. Hypoxic microenvironment and tumor immune response[J]. Journal of International Oncology, 2017,44(1):31-33.
22. [22]
  PARK J E, DUTTA B, TSE S W, GUPTA N, TAN C F, LOW J K, YEOH K W, KON O L, TAM J P, SZE S K. Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift[J]. Oncogene, 2019,38(26):5158-5173. doi: 10.1038/s41388-019-0782-x
23. [23]
  YU C, ZHOU Z G, WANG J, SUN J, LIU W, SUN Y N, KONG B, YANG H, YANG S P. In depth analysis of apoptosis induced by silica coated manganese oxide nanoparticles in vitro[J]. J. Hazard. Mater., 2014,283:519-528.
24. [24]
  PANAGOPOULOS A, ALTMEYER M. The hammer and the dance of cell cycle control[J]. Trends Biochem. Sci., 2021,46(4):301-314. doi: 10.1016/j.tibs.2020.11.002
25. [25]
  WANG X, CHEN S T, HOU Z H, YANG R, ZHANG R W. The effects of curcumin on prostate cancer cell proliferation, invasion, and cell cycle[J]. Journal of Beihua University(Natural Science Edition), 2024,25(6):770-775.
26. [26]
  WANG C, ZHOU H M, KURBONIYON M S, TANG Y P, CAI Z M, NING S F, ZHANG L T, LIANG X Q. Chemodynamic PtMn nanocubes for effective photothermal ROS storm a key anti-tumor therapy in-vivo[J]. Int. J. Nanomed., 2024,19:5045-5056. doi: 10.2147/IJN.S455936
27. [27]
  LI S S, SHANG L, XU B L, WANG S H, GU K, WU Q Y, SUN Y, ZHANG Q H, YANG H L, ZHANG F R, GU L, ZHANG T R, LIU H Y. A nanozyme with photo‐enhanced dual enzyme‐like activities for deep pancreatic cancer therapy[J]. Angew. Chem.‒Int. Edit., 2019,58(36):12624-12631. doi: 10.1002/anie.201904751
28. [28]
  ZHAO Y Y, YANG J, SHAN G, LIU Z Y, CUI A N, WANG A L, CHEN Y W, LIU Y C. Photothermal-enhanced tandem enzyme-like activity of Ag_2-xCu_xS nanoparticles for one-step colorimetric glucose detection in unprocessed human urine[J]. Sens. Actuator B‒Chem., 2020,305127420. doi: 10.1016/j.snb.2019.127420
29. [29]
  ZHANG W X, LI W Y, SHU Y, WANG J H. Manganese-enriched Prussian blue nanohybrids with smaller electrode potential and lower charge transfer resistance to enhance combination therapy[J]. Colloid Surf. B‒Biointerfaces, 2024,241114045. doi: 10.1016/j.colsurfb.2024.114045
30. [30]
  YAO J L, QIU Y, XING J, LI Z H, ZHANG A, TU K, PENG M J, WU X X, YANG F, WU A. Highly-efficient gallium-interference tumor therapy mediated by gallium-enriched Prussian blue nanomedicine[J]. ACS Nano, 2024,18(7):5556-5570.
31. [31]
  LIU Y, QUAN X, LI J, HUO J W, LI X, ZHAO Z P, LI S M, WAN J, LI J, LIU S, WANG T, ZHANG X, GUAN B, WEN R, ZHAO Z W, WANG C R, BAI C L. Liposomes embedded with PEGylated iron oxide nanoparticles enable ferroptosis and combination therapy in cancer[J]. Natl. Sci. Rev., 2023,10(1):246-258.
32. [32]
  WANG P F, SUN S H, BAI G S, ZHANG R Q, LIANG F, ZHANG Y Z. Nano-sized Prussian blue and its analogs for bioimaging and cancer theranostics[J]. Acta Biomater., 2024,176:77-98. doi: 10.1016/j.actbio.2023.12.047
33. [33]
  ZHANG Y J, FENG Y Y, HUANG Y Q, WANG Y F, QIU L, LIU Y L, PENG S S, LI R, KUANG N Z, SHI Q F, SHI Y M, CHEN Y J, JOSHI R, WANG Z G, YUAN K, MIM W P. Tumor-targeted gene silencing IDO synergizes PTT-induced apoptosis and enhances anti-tumor immunity[J]. Front. Immunol., 2020,11968. doi: 10.3389/fimmu.2020.00968
34. [34]
  TAO L, FU R, WANG X P. LL-202, A newly synthesized flavonoid, inhibits tumor growth via inducing G₂/M phase arrest and cell apoptosis in MCF-7 human breast cancer cells in vitro and in vivo[J]. Toxicol. Lett., 2014,228(1):1-12. doi: 10.1016/j.toxlet.2014.04.002
35. [35]
  MUENYI C S, TRIVEDI A P, HELM C W, STATES J C. Cisplatin plus sodium arsenite and hyperthermia induces pseudo-G1 associated apoptotic cell death in ovarian cancer cells[J]. Toxicol. Sci., 2014,139(1):74-82. doi: 10.1093/toxsci/kfu029
36. [36]
  XIE M Z, GONG T J, WANG Y T, LI Z Z, LU M X, LUO Y, MIN L, TU C Q, ZHANG X D, ZENG Q, ZHOU Y. Advancements in photothermal therapy using near-infrared light for bone tumors[J]. Int. J. Mol. Sci., 2024,25(8)4139. doi: 10.3390/ijms25084139
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