Anti-tumor effects of PEGylated-nanoliposomes containing ginger extract in colorectal cancer-bearing mice

Document Type : Original Article

Authors

1 Department of Immunology & Microbiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran

2 Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran

5 Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran

6 Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences, Arak, Iran

Abstract

Objective(s): This study aimed to develop a nanoliposomal formulation containing ginger ethanolic extract with a higher therapeutic effect for cancer treatment. 
Materials and Methods: The present study aimed to prepare PEGylated nanoliposomal ginger through the thin film hydration method plus extrusion. Physicochemical characteristics were evaluated, and the toxicity of the prepared liposomes was assessed using the MTT assay. In addition, tumor size was monitored in colorectal cancer-bearing mice. Also, the anticancer effects of liposomal ginger were evaluated by gene expression assay of Bax and Bcl-2 and cytokines including TNF-α, TGF-β, and IFN-γ by Real-time PCR. Also, cytotoxic T lymphocytes (CTLs) and regulatory T lymphocytes (Treg cells) were counted in spleen and tumor tissue by flow cytometry assay.
Results: The nanoliposomes’ particle size and polydispersity index (PDI) were 94.95 nm and 0.246 nm, respectively. High encapsulation capacity (80 %) confirmed the technique’s efficiency, and the release rate of the extract was 85% at pH 6.5. In addition, this study showed that liposomal ginger at 100 mg/kg/day enhanced the expression of Bax (P<0.05) and IFN-γ (P<0.01) compared with ginger extract in the mouse model. Also, the number of tumor-infiltrating lymphocytes (TILs) and CTLs cell count in tumor tissue showed a significant increase in the LipGin group compared with the Gin group (P<0.05).
Conclusion: Results indicated that the liposomal ginger enhanced the antitumor activity; therefore, the prepared liposomal ginger can be used in future clinical trials.

Keywords

References

1. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Prz Gastroenterol 2019; 14: 89-103.
2. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021;14:101174.
3. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet 2019; 394: 1467-1480.
4. Teixeira S, Carvalho MA, Castanheira EMS. Functionalized liposome and albumin-based systems as carriers for poorly water-soluble anticancer drugs: An updated review. Biomedicines 2022; 10: 486.
5. Benarba B, Pandiella A. Colorectal cancer and medicinal plants: Principle findings from recent studies. Biomed  Pharmacother 2018; 107: 408-423.
6. Makaremi S, Ganji A, Ghazavi A, Mosayebi G. Inhibition of tumor growth in CT-26 colorectal cancer-bearing mice with alcoholic extracts of Curcuma longa and Rosmarinus officinalis. Gene Rep 2021; 22: 101006.
7. Greenwell M, Rahman PK. Medicinal plants: Their use in anticancer treatment. Int J Pharm Sci Res 2015; 6: 4103-4112.
8. Prasad S, Tyagi AK. Ginger and its constituents: Role in prevention and treatment of gastrointestinal cancer. Gastroenterol Res Pract 2015; 2015: 142979.
9. Saeedifar AM, Mosayebi G, Ghazavi A, Ganji A. Synergistic evaluation of ginger and licorice extracts in a mouse model of colorectal cancer. Nutr Cancer 2021;73:1068-1078.
10. Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, et al. Bioactive compounds and bioactivities of ginger (Zingiber officinale roscoe). Foods 2019; 8: 185.
11. Mahomoodally MF, Aumeeruddy MZ, Rengasamy KRR, Roshan S, Hammad S, Pandohee J, et al. Ginger and its active compounds in cancer therapy: From folk uses to nano-therapeutic applications. Semin Cancer Biol 2021; 69: 140-149.
12. Devi VK, Jain N, Valli KS. Importance of novel drug delivery systems in herbal medicines. Pharmacogn Rev 2010; 4: 27-31.
13. Din FU, Aman W, Ullah I, Qureshi OS, Mustapha O, Shafique S, et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomedicine 2017; 12: 7291-7309.
14. Khan Y, Suvarna V. Liposomes containing phytochemicals for cancer treatment-an update. Int J Curr Pharm Res 2016; 9: 20.
15. Mirzavi F, Barati M, Soleimani A, Vakili-Ghartavol R, Jaafari MR, Soukhtanloo M. A review on liposome-based therapeutic approaches against malignant melanoma. Int J Pharm 2021; 599: 120413.
16. Zhang J, Li X, Huang L. Anticancer activities of phytoconstituents and their liposomal targeting strategies against tumor cells and the microenvironment. Adv Drug Deliv Rev 2020;154-155: 245-273.
17. Zheng X, Wu F, Lin X, Shen L, Feng Y. Developments in drug delivery of bioactive alkaloids derived from traditional Chinese medicine. Drug Deliv 2018; 25: 398-416.
18. Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug delivery: Is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem 2016; 27: 2225-2238.
19. Lu L, Xu Q, Wang J, Wu S, Luo Z, Lu W. Drug nanocrystals for active tumor-targeted drug delivery. Pharmaceutics 2022; 14: 797.
20. Giri TK. Breaking the barrier of cancer through liposome loaded with phytochemicals. Curr Drug Deliv 2019; 16: 3-17.
21. Jakoby J, Beuschlein F, Mentz S, Hantel C, Süss R. Liposomal doxorubicin for active targeting: Surface modification of the nanocarrier evaluated in vitro and in vivo: challenges and prospects. Oncotarget 2015; 6: 43698-43711.
22. Ganji A, Farahani I, Palizvan MR, Ghazavi A, Ejtehadifar M, Ebrahimimonfared M, et al. Therapeutic effects of walnut oil on the animal model of multiple sclerosis. Nutr Neurosci 2019; 22: 215-222.
23. Karimi M, Gheybi F, Zamani P, Mashreghi M, Golmohammadzadeh S, Darban SA, et al. Preparation and characterization of stable nanoliposomal formulations of curcumin with high loading efficacy: In vitro and in vivo anti-tumor study. Int J Pharm 2020; 580: 119211.
24. Kemkar K, Lohidasan S, Sathiyanarayanan A, Mahadik K. 6-shogaol from ginger oleoresin loaded liposomes using DMPG-Na as a carrier enhances the in vitro and in vivo anticancer activity. J Appl Pharm Sci 2018; 8: 1-10.
25. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 2016; 99:2 8-51.
26. Gabr SA, Alghadir AH, Ghoniem GA. Biological activities of ginger against cadmium-induced renal toxicity. Saudi J Biol Sci 2019; 26: 382-389.
27. Bakr A, Abdelgayed S, Eltawil O, Bakeer A. Assessment of ginger extract and ginger nanoparticles protective activity against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats. Pakistan Vet J 2019; 39: 479-486.
28. Rousselle C, Clair P, Lefauconnier J-M, Kaczorek M, Scherrmann J-M, Temsamani J. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Mol Pharmacol 2000; 57: 679-686.
29. Odeh F, Ismail SI, Abu-Dahab R, Mahmoud IS, Al Bawab A. Thymoquinone in liposomes: A study of loading efficiency and biological activity towards breast cancer. Drug Deliv 2012; 19: 371-377.
30. Yang C, Liu HZ, Lu WD, Fu ZX. PEG-liposomal oxaliplatin potentialization of antitumor efficiency in a nude mouse tumor-xenograft model of colorectal carcinoma. Oncol Rep 2011; 25: 1621-1628.
31. Kazemi M, Jafarzadeh A, Nemati M, Taghipour F, Oladpour O, Rezayati MT, et al. Zingerone improves the immune responses in an animal model of breast cancer. J Complement Integr Med. 2021; 18: 303-310.
32. Furler RL, Nixon DF, Brantner CA, Popratiloff A, Uittenbogaart CH. TGF-β sustains tumor progression through biochemical and mechanical signal transduction. Cancers 2018; 10: 199.
33. Liu S, Ren J, ten Dijke P. Targeting TGFβ signal transduction for cancer therapy. Signal Transduct Target Ther 2021;6:8.
34. Luo J, Chen X-Q, Li P. The role of TGF-β and its receptors in gastrointestinal cancers. Transl Oncol 2019; 12: 475-484.
35. Wang L, Wang Y, Song Z, Chu J, Qu X. Deficiency of interferon-gamma or its receptor promotes colorectal cancer development. J Interferon Cytokine Res 2015; 35: 273-280.
36. Kosmidis C, Sapalidis K, Koletsa T, Kosmidou M, Efthimiadis C, Anthimidis G, et al. Interferon-γ and colorectal cancer: An up-to date. J Cancer 2018; 9: 232-238.
37. Bai F, Yin Y, Chen T, Chen J, Ge M, Lu Y, et al. Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer. Int J Nanomedicine 2018; 13: 1327-1339.
Iranian Journal of Basic Medical Sciences
Volume 25, Issue 7
July 2022
Pages 890-896

Files

Share

How to cite

Statistics