Research progress on Fe<sub>3</sub>O<sub>4</sub> magnetic nanoparticle-based drug delivery system in the treatment of esophageal cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YANG Kai ^1,2 , WANG Qi ^1,2 , LI Haochi ^1,2 , ZHANG Jinlong ^1,2 , WANG Yaping ^1,2 ,  GOU Yunjiu ² ,  BAI Qizhou ²

1. The First Clinical College of Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding?author：

GOU Yunjiu, Email: gouyunjiu@163.com; BAI Qizhou, Email: baiqizhou1981@163.com

Keywords：

Magnetic nanoparticles; Fe₃O₄; nano-loaded drugs; esophageal cancer; research progress; review

DOI：

10.7507/1007-4848.202407064

Video：

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Abstract Full text Figures/Tables Video References Cited by

Esophageal cancer is a common malignancy with high incidence and poor prognosis. Conventional therapies fail to provide long-term benefits for patients, with postoperative recurrence and metastasis being the primary reasons for treatment failure. With the continuous development of nanomedicine, nanoparticle-based drug delivery has received widespread attention as a novel therapeutic approach. Among them, Fe₃O₄ magnetic nanoparticles have achieved a series of encouraging advancements in the treatment of esophageal cancer, owing to their unique superparamagnetism and biocompatibility. This paper provides a review of the relevant research on Fe₃O₄ magnetic nanoparticle-based drug delivery systems for the treatment of esophageal cancer.

Citation： YANG Kai, WANG Qi, LI Haochi, ZHANG Jinlong, WANG Yaping, GOU Yunjiu, BAI Qizhou. Research progress on Fe₃O₄ magnetic nanoparticle-based drug delivery system in the treatment of esophageal cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2026, 33(7): 1142-1148. doi: 10.7507/1007-4848.202407064 Copy

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2.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3.	Xiao J, Cheng L, Fang T, et al. Nanoparticle-embedded electrospun fiber-covered stent to assist intraluminal photodynamic treatment of oesophageal cancer. Small, 2019, 15(49): e1904979.
4.	Bhatt A, Kamath S, Murthy SC, et al. Multidisciplinary evaluation and management of early stage esophageal cancer. Surg Oncol Clin N Am, 2020, 29(4): 613-630.
5.	Garg PK, Sharma J, Jakhetiya A, et al. Preoperative therapy in locally advanced esophageal cancer. World J Gastroenterol, 2016, 22(39): 8750-8759.
6.	Zhang Y, Zhang Y, Peng L, et al. Research progress on the predicting factors and coping strategies for postoperative recurrence of esophageal cancer. Cells, 2022, 12(1): 114.
7.	徐寅生, 任翔宇, 余夢真, 等. 基于納米技術的藥物遞送策略及其在癌癥治療中的應用. 科學通報, 2023, 68(32): 4346-4372.Xu YS, Ren XY, Yu MZ, et al. Nanotechnology-based drug delivery strategy and its application in cancer therapy. Chin Sci Bull, 2023, 68(32): 4346-4372.
8.	張新雨, 馮亞嬋, 張皓杰, 等. 納米載藥體系在腫瘤耐藥治療中的應用研究進展. 河北科技大學學報, 2022, 43(4): 417-425.Zhang XY, Feng YC, Zhang HJ, et al. Research progress on the application of nano-drug delivery system in tumor drug resistance therapy. J Hebei Univ Sci Tec, 2022, 43(4): 417-425.
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19.	Suk JS, Xu Q, Kim N, et al. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev, 2016, 99(Pt A): 28-51.
20.	Ding Y, Shen SZ, Sun H, et al. Design and construction of polymerized-chitosan coated Fe₃O₄ magnetic nanoparticles and its application for hydrophobic drug delivery. Mater Sci Eng C Mater Biol Appl, 2015, 48: 487-498.
21.	Zhang T, Wang L, He X, et al. Cytocompatibility of pH-sensitive, chitosan-coated Fe₃O₄ nanoparticles in gynecological cells. Front Med (Lausanne), 2022, 9: 799145.
22.	Yuan G, Yuan Y, Xu K, et al. Biocompatible PEGylated Fe₃O₄ nanoparticles as photothermal agents for near-infrared light modulated cancer therapy. Int J Mol Sci, 2014, 15(10): 18776-18788.
23.	邱虎, 洪坤巧, 羅曼, 等. 納米顆粒在晚期食管癌治療中的研究進展. 胃腸病學和肝病學雜志, 2021, 30(8): 935-939.Qiu H, Hong KQ, Luo M, et al. Research progress of nanoparticles in the treatment of advanced esophageal cancer. J Gastr Hepat, 2021, 30(8): 935-939.
24.	Fons P, Gueguen-Dorbes G, Herault JP, et al. Tumor vasculature is regulated by FGF/FGFR signaling-mediated angiogenesis and bone marrow-derived cell recruitment: this mechanism is inhibited by SSR128129E, the first allosteric antagonist of FGFRs. J Cell Physiol, 2015, 230(1): 43-51.
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26.	Gai J, Gao Z, Song L, et al. Contrast-enhanced computed tomography combined with Chitosan-Fe₃O₄ nanoparticles targeting fibroblast growth factor receptor and vascular endothelial growth factor receptor in the screening of early esophageal cancer. Exp Ther Med, 2018, 15(6): 5344-5352.
27.	Karamipour Sh, Sadjadi MS, Farhadyar N. Fabrication and spectroscopic studies of folic acid-conjugated Fe₃O₄@Au core-shell for targeted drug delivery application. Spectrochim Acta A Mol Biomol Spectrosc, 2015, 148: 146-155.
28.	盧琳, 熊素彬. EPR效應在實體瘤靶向治療中的研究進展. 北方藥學, 2014, 11(7): 73.Lu L, Xiong SB. Research progress of EPR effect in targeted therapy of solid tumors. North Pharm, 2014, 11(7): 73.
29.	Subhan MA, Parveen F, Filipczak N, et al. Approaches to improve EPR-based drug delivery for cancer therapy and diagnosis. J Pers Med, 2023, 13(3): 389.
30.	Barenholz Y. Doxil?—The first FDA-approved nano-drug: lessons learned. J Control Release, 2012, 160(2): 117-134.
31.	Leporatti S. Thinking about enhanced permeability and retention effect (EPR). J Pers Med, 2022, 12(8): 1259.
32.	Tietze R, Zaloga J, Unterweger H, et al. Magnetic nanoparticle-based drug delivery for cancer therapy. Biochem Biophys Res Commun, 2015, 468(3): 463-470.
33.	Guo X, Li W, Luo L, et al. External magnetic field-enhanced chemo-photothermal combination tumor therapy via iron oxide nanoparticles. ACS Appl Mater Interfaces, 2017, 9(19): 16581-16593.
34.	Chen Y, Li H, Deng Y, et al. Near-infrared light triggered drug delivery system for higher efficacy of combined chemo-photothermal treatment. Acta Biomater, 2017, 51: 374-392.
35.	Wu L, Chen L, Liu F, et al. Remotely controlled drug release based on iron oxide nanoparticles for specific therapy of cancer. Colloids Surf B Biointerfaces, 2017, 152: 440-448.
36.	Aliabadi M, Shagholani H, Yunessnia Lehi A. Synthesis of a novel biocompatible nanocomposite of graphene oxide and magnetic nanoparticles for drug delivery. Int J Biol Macromol, 2017, 98: 287-291.
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41.	Huang Y, Hsu JC, Koo H, et al. Repurposing ferumoxytol: Diagnostic and therapeutic applications of an FDA-approved nanoparticle. Theranostics, 2022, 12(2): 796-816.
42.	盧啟正, 鄭浩, 沈運麗. 磁性氧化鐵納米顆粒的心血管安全性研究進展. 臨床心血管病雜志, 2022, 38(3): 176-180.Lu QZ, Zheng H, Shen YL. Advances in cardiovascular safety of magnetic iron oxide nanoparticles. J Clin Cardiol, 2022, 38(3): 176-180.
43.	Malhotra N, Lee JS, Liman RAD, et al. Potential toxicity of iron oxide magnetic nanoparticles: a review. Molecules, 2020, 25(14): 3159.
44.	Katsnelson BA, Degtyareva TD, Minigalieva II, et al. Subchronic systemic toxicity and bioaccumulation of Fe₃O₄ nano- and microparticles following repeated intraperitoneal administration to rats. Int J Toxicol, 2011, 30(1): 59-68.
45.	Yang L, Kuang H, Zhang W, et al. Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice. Nanoscale, 2015, 7(2): 625-636.
46.	Yang P, Xu H, Zhang Z, et al. Surface modification affect the biodistribution and toxicity characteristics of iron oxide magnetic nanoparticles in rats. IET Nanobiotechnol, 2018, 12(5): 562-568.
47.	Arami H, Krishnan KM. Intracellular performance of tailored nanoparticle tracers in magnetic particle imaging. J Appl Phys, 2014, 115(17): 17B306.
48.	Nowak-Jary J, Machnicka B. In vivo biodistribution and clearance of magnetic iron oxide nanoparticles for medical applications. Int J Nanomedicine, 2023, 18: 4067-4100.
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1. Domper Arnal MJ, Ferrández Arenas á, Lanas Arbeloa á. Esophageal cancer: risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol, 2015, 21(26): 7933-7943.
2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3. Xiao J, Cheng L, Fang T, et al. Nanoparticle-embedded electrospun fiber-covered stent to assist intraluminal photodynamic treatment of oesophageal cancer. Small, 2019, 15(49): e1904979.
4. Bhatt A, Kamath S, Murthy SC, et al. Multidisciplinary evaluation and management of early stage esophageal cancer. Surg Oncol Clin N Am, 2020, 29(4): 613-630.
5. Garg PK, Sharma J, Jakhetiya A, et al. Preoperative therapy in locally advanced esophageal cancer. World J Gastroenterol, 2016, 22(39): 8750-8759.
6. Zhang Y, Zhang Y, Peng L, et al. Research progress on the predicting factors and coping strategies for postoperative recurrence of esophageal cancer. Cells, 2022, 12(1): 114.
7. 徐寅生, 任翔宇, 余夢真, 等. 基于納米技術的藥物遞送策略及其在癌癥治療中的應用. 科學通報, 2023, 68(32): 4346-4372.Xu YS, Ren XY, Yu MZ, et al. Nanotechnology-based drug delivery strategy and its application in cancer therapy. Chin Sci Bull, 2023, 68(32): 4346-4372.
8. 張新雨, 馮亞嬋, 張皓杰, 等. 納米載藥體系在腫瘤耐藥治療中的應用研究進展. 河北科技大學學報, 2022, 43(4): 417-425.Zhang XY, Feng YC, Zhang HJ, et al. Research progress on the application of nano-drug delivery system in tumor drug resistance therapy. J Hebei Univ Sci Tec, 2022, 43(4): 417-425.
9. 段曉峰, 于振濤. 食管癌新輔助放化療聯合手術與單純手術治療效果的隨機對照試驗Meta分析. 中華胃腸外科雜志, 2017, 20(7): 809-815.Duan XF, Yu ZT. Neoadjuvant chemoradiotherapy combined with operation vs. operation alone for resectable esophageal cancer: Meta-analysis on randomized controlled trials. Chin J Gastrointest Surg, 2017, 20(7): 809-815.
10. 杜益群, 張東生, 倪海燕, 等. 腫瘤熱療用Fe₃O₄磁性納米粒子的生物相容性研究. 南京大學學報(自然科學版), 2006, 42(3): 324-330.Du YQ, Zhang DS, Ni HY, et al. The biocompatibility of Fe₃O₄ magnetic nanoparticles used in tumor hyperthermia. J Nanjing Univ (Natural Science Edition), 2006, 42(3): 324-330.
11. Golombek SK, May JN, Theek B, et al. Tumor targeting via EPR: strategies to enhance patient responses. Adv Drug Deliv Rev, 2018, 130: 17-38.
12. Shi Y, van der Meel R, Chen X, et al. The EPR effect and beyond: strategies to improve tumor targeting and cancer nanomedicine treatment efficacy. Theranostics, 2020, 10(17): 7921-7924.
13. Gao L, Fan K, Yan X. Iron oxide nanozyme: a multifunctional enzyme mimetic for biomedical applications. Theranostics, 2017, 7(13): 3207-3227.
14. Nguyen MD, Tran HV, Xu S, et al. Fe₃O₄ nanoparticles: structures, synthesis, magnetic properties, surface functionalization, and emerging applications. Appl Sci (Basel), 2021, 11(23): 11301.
15. Yang D, Chen Q, Zhang M, et al. PLGA+Fe₃O₄+PFP nanoparticles drug-delivery demonstrates potential anti-tumor effects on tumor cells. Ann Transplant, 2022, 27: e933246.
16. Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine, 2012, 8(2): 147-166.
17. Hilger I, Kaiser WA. Iron oxide-based nanostructures for MRI and magnetic hyperthermia. Nanomedicine (Lond), 2012, 7(9): 1443-1459.
18. Laurent S, Saei AA, Behzadi S, et al. Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges. Expert Opin Drug Deliv, 2014, 11(9): 1449-1470.
19. Suk JS, Xu Q, Kim N, et al. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev, 2016, 99(Pt A): 28-51.
20. Ding Y, Shen SZ, Sun H, et al. Design and construction of polymerized-chitosan coated Fe₃O₄ magnetic nanoparticles and its application for hydrophobic drug delivery. Mater Sci Eng C Mater Biol Appl, 2015, 48: 487-498.
21. Zhang T, Wang L, He X, et al. Cytocompatibility of pH-sensitive, chitosan-coated Fe₃O₄ nanoparticles in gynecological cells. Front Med (Lausanne), 2022, 9: 799145.
22. Yuan G, Yuan Y, Xu K, et al. Biocompatible PEGylated Fe₃O₄ nanoparticles as photothermal agents for near-infrared light modulated cancer therapy. Int J Mol Sci, 2014, 15(10): 18776-18788.
23. 邱虎, 洪坤巧, 羅曼, 等. 納米顆粒在晚期食管癌治療中的研究進展. 胃腸病學和肝病學雜志, 2021, 30(8): 935-939.Qiu H, Hong KQ, Luo M, et al. Research progress of nanoparticles in the treatment of advanced esophageal cancer. J Gastr Hepat, 2021, 30(8): 935-939.
24. Fons P, Gueguen-Dorbes G, Herault JP, et al. Tumor vasculature is regulated by FGF/FGFR signaling-mediated angiogenesis and bone marrow-derived cell recruitment: this mechanism is inhibited by SSR128129E, the first allosteric antagonist of FGFRs. J Cell Physiol, 2015, 230(1): 43-51.
25. Takahashi O, Komaki R, Smith PD, et al. Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis. Clin Cancer Res, 2012, 18(6): 1641-1654.
26. Gai J, Gao Z, Song L, et al. Contrast-enhanced computed tomography combined with Chitosan-Fe₃O₄ nanoparticles targeting fibroblast growth factor receptor and vascular endothelial growth factor receptor in the screening of early esophageal cancer. Exp Ther Med, 2018, 15(6): 5344-5352.
27. Karamipour Sh, Sadjadi MS, Farhadyar N. Fabrication and spectroscopic studies of folic acid-conjugated Fe₃O₄@Au core-shell for targeted drug delivery application. Spectrochim Acta A Mol Biomol Spectrosc, 2015, 148: 146-155.
28. 盧琳, 熊素彬. EPR效應在實體瘤靶向治療中的研究進展. 北方藥學, 2014, 11(7): 73.Lu L, Xiong SB. Research progress of EPR effect in targeted therapy of solid tumors. North Pharm, 2014, 11(7): 73.
29. Subhan MA, Parveen F, Filipczak N, et al. Approaches to improve EPR-based drug delivery for cancer therapy and diagnosis. J Pers Med, 2023, 13(3): 389.
30. Barenholz Y. Doxil?—The first FDA-approved nano-drug: lessons learned. J Control Release, 2012, 160(2): 117-134.
31. Leporatti S. Thinking about enhanced permeability and retention effect (EPR). J Pers Med, 2022, 12(8): 1259.
32. Tietze R, Zaloga J, Unterweger H, et al. Magnetic nanoparticle-based drug delivery for cancer therapy. Biochem Biophys Res Commun, 2015, 468(3): 463-470.
33. Guo X, Li W, Luo L, et al. External magnetic field-enhanced chemo-photothermal combination tumor therapy via iron oxide nanoparticles. ACS Appl Mater Interfaces, 2017, 9(19): 16581-16593.
34. Chen Y, Li H, Deng Y, et al. Near-infrared light triggered drug delivery system for higher efficacy of combined chemo-photothermal treatment. Acta Biomater, 2017, 51: 374-392.
35. Wu L, Chen L, Liu F, et al. Remotely controlled drug release based on iron oxide nanoparticles for specific therapy of cancer. Colloids Surf B Biointerfaces, 2017, 152: 440-448.
36. Aliabadi M, Shagholani H, Yunessnia Lehi A. Synthesis of a novel biocompatible nanocomposite of graphene oxide and magnetic nanoparticles for drug delivery. Int J Biol Macromol, 2017, 98: 287-291.
37. Sohail A, Ahmad Z, Bég OA, et al. A review on hyperthermia via nanoparticle-mediated therapy. Bull Cancer, 2017, 104(5): 452-461.
38. Estelrich J, Busquets MA. Iron oxide nanoparticles in photothermal therapy. Molecules, 2018, 23(7): 1567.
39. 王煦漫, 古宏晨, 楊正強, 等. 磁熱療用Fe₃O₄在交變磁場中的熱效應. 上海交通大學學報, 2005, 39(2): 275-278.Wang XM, Gu HC, Yang ZQ, et al. The heat effect of magnetite for hyperthermia under alternating magnetic field. J Shanghai Jiaotong Univ, 2005, 39(2): 275-278.
40. Chu M, Shao Y, Peng J, et al. Near-infrared laser light mediated cancer therapy by photothermal effect of Fe₃O₄ magnetic nanoparticles. Biomaterials, 2013, 34(16): 4078-4088.
41. Huang Y, Hsu JC, Koo H, et al. Repurposing ferumoxytol: Diagnostic and therapeutic applications of an FDA-approved nanoparticle. Theranostics, 2022, 12(2): 796-816.
42. 盧啟正, 鄭浩, 沈運麗. 磁性氧化鐵納米顆粒的心血管安全性研究進展. 臨床心血管病雜志, 2022, 38(3): 176-180.Lu QZ, Zheng H, Shen YL. Advances in cardiovascular safety of magnetic iron oxide nanoparticles. J Clin Cardiol, 2022, 38(3): 176-180.
43. Malhotra N, Lee JS, Liman RAD, et al. Potential toxicity of iron oxide magnetic nanoparticles: a review. Molecules, 2020, 25(14): 3159.
44. Katsnelson BA, Degtyareva TD, Minigalieva II, et al. Subchronic systemic toxicity and bioaccumulation of Fe₃O₄ nano- and microparticles following repeated intraperitoneal administration to rats. Int J Toxicol, 2011, 30(1): 59-68.
45. Yang L, Kuang H, Zhang W, et al. Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice. Nanoscale, 2015, 7(2): 625-636.
46. Yang P, Xu H, Zhang Z, et al. Surface modification affect the biodistribution and toxicity characteristics of iron oxide magnetic nanoparticles in rats. IET Nanobiotechnol, 2018, 12(5): 562-568.
47. Arami H, Krishnan KM. Intracellular performance of tailored nanoparticle tracers in magnetic particle imaging. J Appl Phys, 2014, 115(17): 17B306.
48. Nowak-Jary J, Machnicka B. In vivo biodistribution and clearance of magnetic iron oxide nanoparticles for medical applications. Int J Nanomedicine, 2023, 18: 4067-4100.
49. Ghosh SC, Neslihan Alpay S, Klostergaard J. CD44: a validated target for improved delivery of cancer therapeutics. Expert Opin Ther Targets, 2012, 16(7): 635-650.
50. Mattheolabakis G, Milane L, Singh A, et al. Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine. J Drug Target, 2015, 23(7-8): 605-618.
51. Skandalis SS, Gialeli C, Theocharis AD, et al. Advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan-CD44 interactions and signaling in cancer. Adv Cancer Res, 2014, 123: 277-317.
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Research progress on Fe₃O₄ magnetic nanoparticle-based drug delivery system in the treatment of esophageal cancer