Skip to main content

Advertisement

SpringerLink
Log in

Application of temperature-sensitive liquid embolic agent loaded with oxaliplatin in the TACE procedure for rabbit VX2 gastric cancer

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data generated and analyzed during the current study are available from the corresponding authors upon reasonable request.

Abbreviations

TACE:

Transcatheter arterial chemoembolization

DSA:

Digital subtraction angiography

TempSLE:

Temperature-sensitive liquid embolic agent

pNIPAAm:

Poly-N-isopropylacrylamide

TempSLE/Oxa:

TempSLE loaded with oxaliplatin

Ioil/Oxa:

Iodinated oil loaded with oxaliplatin

NS:

Normal saline

LC–MS/MS:

Liquid chromatography-tandem mass spectrometry

HE:

Hematoxylin-eosin

VEGF:

Vascular endothelial growth factor

PCNA:

Proliferating cell nuclear antigen

References

  1. 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;71:209–49.

    Article  PubMed  Google Scholar 

  2. Mo DC, Qin L, Ye LJ. Neoadjuvant docetaxel, oxaliplatin, and S-1 in resectable advanced gastric cancer. J Clin Oncol. 2021;39:3883–4.

    Article  CAS  PubMed  Google Scholar 

  3. Li S, Yu W, Xie F, et al. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. Nat Commun. 2023;14:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2022;20:167–92.

    Article  CAS  Google Scholar 

  5. Joharatnam-Hogan N, Shiu KK, Khan K. Challenges in the treatment of gastric cancer in the older patient. Cancer Treat Rev. 2020;85:101980.

    Article  PubMed  Google Scholar 

  6. Liang L, Li C, Wang MD, et al. Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma. J Hematol Oncol. 2021;14:165.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kim JH, Yoon HK, Kim SY, et al. Transcatheter arterial chemoembolization vs. chemoinfusion for unresectable hepatocellular carcinoma in patients with major portal vein thrombosis. Aliment Pharmacol Ther. 2009;29:1291–8.

    Article  CAS  PubMed  Google Scholar 

  8. Farinati F, Rinaldi M, Gianni S, et al. Transcatheter arterial chemoembolization in hepatocellular carcinoma. Hepatology (Baltimore, MD). 1998;28:1441–3.

    Article  CAS  PubMed  Google Scholar 

  9. Li N, Wang G, Duan G, et al. Clinical observation of transcatheter arterial chemoembolization in super-aged patients with advanced gastric cancer. Support Care Cancer. 2022;30:1441–50.

    Article  PubMed  Google Scholar 

  10. Peng D, Zhang B, Yuan C, et al. Gastric transcatheter chemoembolization can resolve advanced gastric cancer presenting with obstruction. Front Surg. 2022;9:1004064.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Golfieri R, Giampalma E, Renzulli M, et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014;111:255–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Overstreet DJ, Lee EJ, Pal A, et al. In situ crosslinking temperature-responsive hydrogels with improved delivery, swelling, and elasticity for endovascular embolization. J Biomed Mater Res B Appl Biomater. 2022;110:1911–21.

    Article  CAS  PubMed  Google Scholar 

  13. Din FU, Kim DW, Choi JY, et al. Irinotecan-loaded double-reversible thermogel with improved antitumor efficacy without initial burst effect and toxicity for intramuscular administration. Acta Biomater. 2017;54:239–48.

    Article  CAS  PubMed  Google Scholar 

  14. Xing R, Mustapha O, Ali T, et al. Development, characterization, and evaluation of SLN-loaded thermoresponsive hydrogel system of topotecan as biological macromolecule for colorectal delivery. Biomed Res Int. 2021;2021:9968602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Din FU, Choi JY, Kim DW, et al. Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration. Drug Delivery. 2017;24:502–10.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Moghadam S, Larson RG. Assessing the efficacy of poly(N-isopropylacrylamide) for drug delivery applications using molecular dynamics simulations. Mol Pharm. 2017;14:478–91.

    Article  CAS  PubMed  Google Scholar 

  17. Batool S, Sohail S, Ud Din F, et al. A detailed insight of the tumor targeting using nanocarrier drug delivery system. Drug Delivery. 2023;30:2183815.

    Article  PubMed  PubMed Central  Google Scholar 

  18. He Y, Yuan T, Wang X, et al. Temperature sensitive hydrogel for preoperative treatment of renal carcinoma. Mater Sci Eng C Mater Biol Appl. 2020;111:110798.

    Article  CAS  PubMed  Google Scholar 

  19. Bi Y, Ren K, Ren J, et al. Oxaliplatin eluting CalliSpheres microspheres for the treatment of unresectable or recurrent hepatocellular carcinoma. Front Pharmacol. 2022;13:923585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bi Y, Li F, Ren J, et al. The safety and efficacy of oxaliplatin-loaded drug-eluting beads transarterial chemoembolization for the treatment of unresectable or advanced lung cancer. Front Pharmacol. 2022;13:1079707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lym JS, Nguyen QV, da Ahn W, et al. Sulfamethazine-based pH-sensitive hydrogels with potential application for transcatheter arterial chemoembolization therapy. Acta Biomater. 2016;41:253–63.

    Article  CAS  PubMed  Google Scholar 

  22. Zhao H, Zheng C, Feng G, et al. Temperature-sensitive poly(N-isopropylacrylamide-co-butyl methylacrylate) nanogel as an embolic agent: distribution, durability of vascular occlusion, and inflammatory reactions in the renal artery of rabbits. AJNR Am J Neuroradiol. 2013;34:169–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ma J, Wang B, Shao H, et al. Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment. Drug Delivery. 2022;29:1457–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lanzalaco S, Armelin E. Poly(N-isopropylacrylamide) and copolymers: a review on recent progresses in biomedical applications. Gels (Basel, Switzerland). 2017;3.

  25. Narayanaswamy R, and Torchilin VP. Hydrogels and their applications in targeted drug delivery. Molecules (Basel, Switzerland). 2019;24.

  26. Kikuchi IS, Cardoso Galante RS, Dua K, et al. Hydrogel based drug delivery systems: a review with special emphasis on challenges associated with decontamination of hydrogels and biomaterials. Curr Drug Deliv. 2017;14:917–25.

    Article  CAS  PubMed  Google Scholar 

  27. Khan MW, Zou C, Hassan S, et al. Cisplatin and oleanolic acid co-loaded pH-sensitive CaCO(3) nanoparticles for synergistic chemotherapy. RSC Adv. 2022;12:14808–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang ZS, Li HZ, Ma C, et al. Conventional versus drug-eluting beads chemoembolization for infiltrative hepatocellular carcinoma: a comparison of efficacy and safety. BMC Cancer. 2019;19:1162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Qian K, Ma Y, Wan J, et al. The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor. J Control Release. 2015;212:41–9.

    Article  CAS  PubMed  Google Scholar 

  30. Wei W, Li H, Yin C, et al. Research progress in the application of in situ hydrogel system in tumor treatment. Drug Delivery. 2020;27:460–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Din FU, Aman W, Ullah I, et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomed. 2017;12:7291–309.

    Article  Google Scholar 

  32. Tong H, Duan LG, Zhou HY, et al. Modification of the method to establish a hepatic VX2 carcinoma model in rabbits. Oncol Lett. 2018;15:5333–8.

    PubMed  PubMed Central  Google Scholar 

  33. Zhang L, Sun JH, Ji JS, et al. Imaging changes and clinical complications after drug-eluting bead versus conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: multicenter study. AJR Am J Roentgenol. 2021;217:933–43.

    Article  PubMed  Google Scholar 

  34. Partyka R, Gonciarz M, Jałowiecki P, et al. VEGF and metalloproteinase 2 (MMP 2) expression in gastric cancer tissue. Med Sci Monit. 2012;18:Br130-134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fu JD, Yao JJ, Wang H, et al. Effects of EGCG on proliferation and apoptosis of gastric cancer SGC7901 cells via down-regulation of HIF-1α and VEGF under a hypoxic state. Eur Rev Med Pharmacol Sci. 2019;23:155–61.

    PubMed  Google Scholar 

  36. Zhang Q, Wu J, Bai X, et al. Evaluation of intra-tumoral vascularization in hepatocellular carcinomas. Front Med. 2020;7:584250.

    Article  Google Scholar 

  37. Li N, Deng W, Ma J, et al. Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Med Oncol (Northwood, London, England). 2015;32:433.

    Article  Google Scholar 

Download references

Acknowledgements

We thank the Medical Research Center of the First Affiliated Hospital of Zhengzhou University for the technical support.

Funding

This work was supported by Central Plains Scholars Workstation in 2022 (workstation numbers ZYGZZ2022087; grant numbers 234400510027) and Central Plains Scholars Workstation in 2021 (workstation numbers ZYGZZ2021054; grant numbers 224400510024).

Author information

Author notes

  1. Yahua Li and Xiaoyong Ge contributed equally to this work.

Authors and Affiliations

  1. Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China

    Yahua Li, Xiaoyong Ge, Zongming Li, Zihe Zhou, Kunpeng Wu, Yifan Li, Jianzhuang Ren, Xinwei Han & Kewei Ren

  2. Department of Peripheral Vascular, Zhoukou Chinese Medicine Hospital, Zhoukou, 466000, People’s Republic of China

    Tengfei Ji & Changran Wang

  3. Department of Oncology, Yellow River Sanmenxia Hospital, Sanmenxia, 472000, People’s Republic of China

    Kefeng Guo

  4. Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, 450052, People’s Republic of China

    Xinwei Han

  5. Interventional Institute of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China

    Xinwei Han

  6. Engineering Technology Research Center for Minimally Invasive, Interventional Tumors of Henan Province, Zhengzhou, 450052, Henan, China

    Kewei Ren

Authors
  1. Yahua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoyong Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zongming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zihe Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kunpeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yifan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tengfei Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Changran Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kefeng Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jianzhuang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xinwei Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kewei Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xinwei Han and Kewei Ren contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Yahua Li, Xiaoyong Ge, Zongming Li, Zihe Zhou, Kunpeng Wu, Yifan Li, Tengfei Ji, Changran Wang, Kefeng Guo, and Jianzhuang Ren. The first draft of the manuscript was written by Yahua Li and Xiaoyong Ge. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xinwei Han or Kewei Ren.

Ethics declarations

Ethics approval and consent to participate

All institutional and national guidelines for the care and use of laboratory animals were followed.

Consent for publication

Consent has been asked where appropriate.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Ge, X., Li, Z. et al. Application of temperature-sensitive liquid embolic agent loaded with oxaliplatin in the TACE procedure for rabbit VX2 gastric cancer. Drug Deliv. and Transl. Res. 14, 705–717 (2024). https://doi.org/10.1007/s13346-023-01425-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-023-01425-5

Keywords

Search

Navigation