Skip to main content

Advertisement

SpringerLink
Log in

PEGylated Lecithin–Chitosan–Folic Acid Nanoparticles as Nanocarriers of Allicin for In Vitro Controlled Release and Anticancer Effects

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

In this study, chitosan-lecithin nanoparticles modified with polyethylene glycol (PEG) and folic acid (FA) were used to deliver allicin (AC) to colon cancer cells. AC-loaded polyethylene glycol (PEG) and folic acid (FA)-modified chitosan-lecithin nanoparticles (AC-PLCF-NPs) were fabricated via self-assembling procedure. HPLC for AC encapsulation and FA binding, MTT for viability assay, ABTS and DPPH for antioxidant capacity, disc diffusion, MIC and MBC for antibacterial assay, qPCR and AO/PI staining for apoptotic, and CAM assay for angiogenesis effects of AC-PLCF-NPs were used. AC-PLCF-NPs (113.55 nm) were synthesized as single dispersed (PDI: 0.28) and stable (ZP: + 33.18 mV) with 81% AC encapsulation and 48% FA binding. The antioxidant power of AC-PLCF-NPs was confirmed by inhibiting free radicals ABTS (74.25 µg/mL) and DPPH (366.214 µg/mL) and its antibacterial capacity with very high inhibitory effects against gram-negative bacterial strains. MTT results showed higher toxicity of AC-PLCF-NPs (68.06 µg/mL) compared to AC (171.45 µg/mL). Increased expression of caspase 3 and 9 genes showed activation of the intrinsic apoptosis pathway in treated cells, and on the other hand, reduction of vascular and embryonic growth factors in CAM model confirmed the anti-angiogenesis effects of AC-PLCF-NPs. AC-PLCF-NPs can be suggested as a promising therapeutic agent for studies in the field of colon cancer treatment.

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
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

Not applicable.

References

  1. Al-Ishaq, R. K., Overy, A. J., & Büsselberg, D. (2020). Phytochemicals and gastrointestinal cancer: Cellular mechanisms and effects to change cancer progression. Biomolecules, 10(1), 105.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sarvizadeh, M., et al. (2021). Allicin and digestive system cancers: From chemical structure to its therapeutic opportunities. Frontiers in Oncology, 563.

  3. Lau, H. C. H., et al. (2020). Organoid models of gastrointestinal cancers in basic and translational research. Nature reviews Gastroenterology & hepatology, 17(4), 203–222.

    Google Scholar 

  4. Sitarz, R., et al. (2018). Gastric cancer: Epidemiology, prevention, classification, and treatment. Cancer Management Research, 10, 239–248.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pourhanifeh, M. H., et al. (2020). Autophagy-related microRNAs: Possible regulatory roles and therapeutic potential in and gastrointestinal cancers. Pharmacological Research, 161, 105133.

    CAS  PubMed  Google Scholar 

  6. Parikh, A. R., et al. (2020). Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers. Clinical Cancer Research, 26(8), 1877–1885.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Moriarty, R. M., Naithani, R., & Surve, B. (2007). Organosulfur compounds in cancer chemoprevention. Mini Reviews in Medicinal Chemistry, 7(8), 827–838.

    CAS  PubMed  Google Scholar 

  8. Nagini, S. (2008). Cancer chemoprevention by garlic and its organosulfur compounds-panacea or promise? Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 8(3), 313–321.

  9. Walag, A. M. P., et al. (2020). Health benefits of organosulfur compounds. Functional Foods and Nutraceuticals 445–472. Springer.

    Google Scholar 

  10. Xiao, D., et al. (2005). Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells. Molecular Cancer Therapeutics, 4(9), 1388–1398.

    CAS  PubMed  Google Scholar 

  11. Miękus, N., et al. (2020). Health benefits of plant-derived sulfur compounds, glucosinolates, and organosulfur compounds. Molecules, 25(17), 3804.

    PubMed  PubMed Central  Google Scholar 

  12. El-Bayoumy, K., et al. (2006). Cancer chemoprevention by garlic and garlic-containing sulfur and selenium compounds. The Journal of Nutrition, 136(3), 864S-869S.

    CAS  PubMed  Google Scholar 

  13. Shafeeque, K., & Hashim, K. (2018). Comparative anti-angiogenesis study between allicin nanoparticle and normal allicin from garlic (Allium sativum Linn). Europe Journal of Experimental Biology, 8, 27.

    CAS  Google Scholar 

  14. Lang, A., et al. (2004). Allicin inhibits spontaneous and TNF-α induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells. Clinical Nutrition, 23(5), 1199–1208.

    CAS  PubMed  Google Scholar 

  15. Sun, L., & Wang, X. (2003). Effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells. World Journal of Gastroenterology, 9(9), 1930.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Arditti, F. D., et al. (2005). Apoptotic killing of B-chronic lymphocytic leukemia tumor cells by allicin generated in situ using a rituximab-alliinase conjugate. Molecular Cancer Therapeutics, 4(2), 325–332.

    CAS  PubMed  Google Scholar 

  17. Jakubikova, J., & Sedlak, J. (2006). Garlic-derived organosulfides induce cytotoxicity, apoptosis, cell cycle arrest and oxidative stress in human colon carcinoma cell lines. Neoplasma, 53(3), 191–199.

    CAS  PubMed  Google Scholar 

  18. Zarei, B., Tabrizi, M. H., & Rahmati, A. (2022). PEGylated lecithin-chitosan nanoparticle–encapsulated alphα-terpineol for in vitro anticancer effects. An Official Journal of the American Association of Pharmaceutical Scientists, 23(4), 1–14.

    Google Scholar 

  19. Perez-Ruiz, A. G., et al. (2018). Lecithin–chitosan–TPGS nanoparticles as nanocarriers of (−)-epicatechin enhanced its anticancer activity in breast cancer cells. RSC Advances, 8(61), 34773–34782.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Khan, M. M., et al. (2019). Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin. Drug Delivery, 26(1), 765–772.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Mandal, B., et al. (2013). Core–shell-type lipid–polymer hybrid nanoparticles as a drug delivery platform. Nanomedicine: Nanotechnology, Biology and Medicine, 9(4), 474–491.

    CAS  PubMed  Google Scholar 

  22. Rahmati, A., et al. (2022). Fabrication and assessment of folic acid conjugated-chitosan modified PLGA nanoparticle for delivery of alpha terpineol in colon cancer. Journal of Biomaterials Science, Polymer Edition, 33(10), 1289–1307.

  23. Mengoni, T., et al. (2017). A Chitosan—based liposome formulation enhances the in vitro wound healing efficacy of substance P neuropeptide. Pharmaceutics, 9(4), 56.

    PubMed  PubMed Central  Google Scholar 

  24. Kouchakzadeh, H., et al. (2010). Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology. An Official Journal of the American Association of Pharmaceutical Scientists, 11(3), 1206–1211.

    CAS  Google Scholar 

  25. Veronese, F. M., & Pasut, G. (2005). PEGylation, successful approach to drug delivery. Drug Discovery Today, 10(21), 1451–1458.

    CAS  PubMed  Google Scholar 

  26. Gavas, S., Quazi, S., & Karpiński, T. M. (2021). Nanoparticles for cancer therapy: Current progress and challenges. Nanoscale Research Letters, 16(1), 1–21.

    Google Scholar 

  27. Hosseini, S. F., et al. (2013). Two-step method for encapsulation of oregano essential oil in chitosan nanoparticles: Preparation, characterization and in vitro release study. Carbohydrate Polymers, 95(1), 50–56.

    CAS  PubMed  Google Scholar 

  28. Salopek, B., Krasic, D., & Filipovic, S. (1992). Measurement and application of zeta-potential. Rudarsko-geolosko-naftni zbornik, 4(1), 147.

    Google Scholar 

  29. Soe, Z. C., et al. (2019). Folate-targeted nanostructured chitosan/chondroitin sulfate complex carriers for enhanced delivery of bortezomib to colorectal cancer cells. Asian Journal of Pharmaceutical Sciences, 14(1), 40–51.

    PubMed  Google Scholar 

  30. Chen, H., et al. (2018). Allicin inhibits proliferation and invasion in vitro and in vivo via SHP-1-mediated STAT3 signaling in cholangiocarcinoma. Cellular Physiology and Biochemistry, 47(2), 641–653.

    CAS  PubMed  Google Scholar 

  31. Thurston, D.E., & I. Pysz, (2021). Chemistry and pharmacology of anticancer drugs. CRC press. eBook.

  32. Harlev, E., et al. (2012). Anticancer attributes of desert plants: A review. Anti-Cancer Drugs, 23(3), 255–271.

    CAS  PubMed  Google Scholar 

  33. Souid, S., et al. (2017). Allium roseum L. extract exerts potent suppressive activities on chronic myeloid leukemia K562 cell viability through the inhibition of BCR-ABL, PI3K/Akt, and ERK1/2 pathways and the abrogation of VEGF secretion. Nutrition and Cancer, 69(1), 117–130.

    PubMed  Google Scholar 

  34. Zou, X., et al. (2016). Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway. Journal of Pharmacological Sciences, 131(4), 233–240.

    CAS  PubMed  Google Scholar 

  35. Luo, R., et al. (2016). The mechanism in gastric cancer chemoprevention by allicin. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 16(7), 802–809.

    CAS  Google Scholar 

  36. Oommen, S., et al. (2004). Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. European Journal of Pharmacology, 485(1–3), 97–103.

    CAS  PubMed  Google Scholar 

  37. Park, S.-Y., et al. (2005). Caspase-independent cell death by allicin in human epithelial carcinoma cells: Involvement of PKA. Cancer Letters, 224(1), 123–132.

    CAS  PubMed  Google Scholar 

  38. Müller, A., et al. (2016). Allicin induces thiol stress in bacteria through S-allylmercapto modification of protein cysteines. Journal of Biological Chemistry, 291(22), 11477–11490.

    PubMed  PubMed Central  Google Scholar 

  39. Ma, Q., et al. (2020). Self-Assembled chitosan/phospholipid nanoparticles: From fundamentals to preparation for advanced drug delivery. Drug Delivery, 27(1), 200–215.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Maiti, R., et al. (2018). Bovine serum albumin nanoparticles constructing procedures on anticancer activities. International Journal of Advanced Research Biology Science, 5(4), 226–239.

    CAS  Google Scholar 

  41. Mariyam, M., et al. (2018). Dendrimers: General aspects, applications and structural exploitations as prodrug/drug-delivery vehicles in current medicine. Mini Reviews in Medicinal Chemistry, 18(5), 439–457.

    CAS  PubMed  Google Scholar 

  42. Barbieri, S., et al. (2013). Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: Loading, enzyme-trigger release and cell uptake. Journal of Controlled Release, 167(3), 276–283.

    CAS  PubMed  Google Scholar 

  43. Hafner, A., et al. (2011). Short- and long-term stability of lyophilised melatonin-loaded lecithin/chitosan nanoparticles. Chemical and Pharmaceutical Bulletin, 59(9), 1117–1123.

    CAS  PubMed  Google Scholar 

  44. Nadeem, M. S., et al. (2021). Allicin, an antioxidant and neuroprotective agent, ameliorates cognitive impairment. Antioxidants, 11(1), 87.

    PubMed  PubMed Central  Google Scholar 

  45. Kelsey, N. A., Wilkins, H. M., & Linseman, D. A. (2010). Nutraceutical antioxidants as novel neuroprotective agents. Molecules, 15(11), 7792–7814.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kurusu, T., Kuchitsu, K., & Tada, Y. (2015). Plant signaling networks involving Ca2+ and Rboh/Nox-mediated ROS production under salinity stress. Frontiers in Plant Science, 6, 427.

    PubMed  PubMed Central  Google Scholar 

  47. Pendyala, S., & Natarajan, V. (2010). Redox regulation of Nox proteins. Respiratory physiology & neurobiology, 174(3), 265–271.

    CAS  Google Scholar 

  48. Gruhlke, M. C., & Slusarenko, A. J. (2012). The biology of reactive sulfur species (RSS). Plant Physiology and Biochemistry, 59, 98–107.

    CAS  PubMed  Google Scholar 

  49. Cutler, R., & Wilson, P. (2004). Antibacterial activity of a new, stable, aqueous extract of allicin against methicillin-resistant Staphylococcus aureus. British Journal of Biomedical Science, 61(2), 71–74.

    CAS  PubMed  Google Scholar 

  50. Zainal, M., et al. (2021). The antimicrobial and antibiofilm properties of allicin against Candida albicans and Staphylococcus aureus–A therapeutic potential for denture stomatitis. The Saudi Dental Journal, 33(2), 105–111.

    PubMed  Google Scholar 

  51. Abbasi, N., et al. (2021). Cerium oxide nanoparticles-loaded on chitosan for the investigation of anticancer properties. Materials Technology, 37(10), 1439–1449.

  52. Hu, X., et al. (2018). Thymoquinone augments cisplatin-induced apoptosis on esophageal carcinoma through mitigating the activation of JAK2/STAT3 pathway. Digestive Diseases and Sciences, 63(1), 126–134.

    CAS  PubMed  Google Scholar 

  53. Ji, Y., et al. (2012). Angiotensin II induces angiogenic factors production partly via AT1/JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells. Cellular Physiology and Biochemistry, 29(5–6), 863–874.

    CAS  PubMed  Google Scholar 

  54. Wang, W., et al. (2016). Allicin inhibits lymphangiogenesis through suppressing activation of vascular endothelial growth factor (VEGF) receptor. The Journal of nutritional biochemistry, 29, 83–89.

    CAS  PubMed  Google Scholar 

  55. Teleanu, R. I., et al. (2020). Tumor angiogenesis and anti-angiogenic strategies for cancer treatment. Journal of Clinical Medicine, 9(1), 84.

    CAS  Google Scholar 

  56. Maeda, H. (2001). The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting. Advances in Enzyme Regulation, 41, 189–207.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Islamic Azad University, Mashhad, Iran, and thus is appreciated by the author.

Funding

This research was performed at personal expense in the laboratory of the Islamic Azad University of Mashhad.

Author information

Authors and Affiliations

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

    Seyed Isaac Hashemy, Hamed Amiri & Hossein Hosseini

  2. Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran

    Farzaneh Sadeghzadeh

  3. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran

    Muslem Mohammed Mosa Jaseem & Masoud Homayouni Tabrizi

Authors
  1. Seyed Isaac Hashemy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hamed Amiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hossein Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Farzaneh Sadeghzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Muslem Mohammed Mosa Jaseem
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masoud Homayouni Tabrizi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally.

Corresponding author

Correspondence to Masoud Homayouni Tabrizi.

Ethics declarations

Ethical Approval

Not required.

Consent to Participate

All authors have their consent to participate.

Consent to Publish

All authors have their consent to publish their work.

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

Hashemy, S.I., Amiri, H., Hosseini, H. et al. PEGylated Lecithin–Chitosan–Folic Acid Nanoparticles as Nanocarriers of Allicin for In Vitro Controlled Release and Anticancer Effects. Appl Biochem Biotechnol 195, 4036–4052 (2023). https://doi.org/10.1007/s12010-022-04310-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-022-04310-y

Keywords

Search

Navigation