Abstract

This study explores the pharmacological investigation and anti-cancer potential of folate-modified Gellan gum nanoparticles, focusing on their impact on cancer cells through p53 activation and the inhibition of the mTOR/PI3K pathway. The nanoparticles were meticulously characterized using advanced techniques, including Nuclear Magnetic Resonance (NMR) and Fourier-Transform Infrared Spectroscopy (FTIR) to ensure structural integrity. Additionally, drug release kinetics, particle size, zeta potential, and entrapment efficiency were assessed to understand the formulation's physicochemical properties. Anti-cancer efficacy was evaluated through Sulforhodamine B (SRB) assay, demonstrating a significant reduction in cell viability upon exposure to the folate-modified Gellan gum nanoparticles. The p53 assay revealed an upregulation of the tumor suppressor protein, indicating activation of the intrinsic apoptotic pathway. Concurrently, the mTOR assay demonstrated inhibition of the mTOR/PI3K signaling pathway, further supporting the anti-cancer potential of the nanoparticles. Comprehensive characterization studies corroborated the efficacy findings, with NMR and FTIR confirming the successful modification of Gellan gum. The nanoparticle formulation exhibited controlled drug release, optimal particle size, desirable zeta potential, and high entrapment efficiency, collectively contributing to its potential as an effective anti-cancer agent. In conclusion, this research provides a thorough investigation into the anti-cancer potential of folate-modified Gellan gum nanoparticles. The synergy of SRB, p53, and mTOR assays, coupled with detailed characterization parameters, establishes a comprehensive understanding of the formulation's efficacy. These findings support the development of Gellan gum nanoparticles as a promising candidate for targeted cancer therapy, warranting further exploration and clinical translation.

Keywords

• Folic Acid,
• Gellan Gum,
• P53,
• Mtor,
• SRB,
• Tumor Targeting,
• Drug Delivery

References

• Kingsley, J. D., Dou, H., Morehead, J., Rabinow, B., Gendelman, H. E., & Destache, C. J. (2006). Nanotechnology: a focus on nanoparticles as a drug delivery system. Journal of Neuroimmune Pharmacology, 1(3), 340-350.
• Torchilin, V. P. (2000). Drug targeting. European Journal of Pharmaceutical Sciences, 11, S81-S91. doi:10.1016/s0928-0987(00)00166-4
• Gerber, D. E. (2008). Targeted therapies: a new generation of cancer treatments. Am Fam Physician.77, 311–319
• Mimeault, M., Hauke, R., & Batra, S. (2007). Recent Advances on the Molecular Mechanisms Involved in the Drug Resistance of Cancer Cells and Novel Targeting Therapies. Clinical Pharmacology & Therapeutics, 83(5), 673-691. doi:10.1038/sj.clpt.6100296
• Vila, A., Sánchez, A., Tobı́o, M., Calvo, P., & Alonso, M. (2002). Design of biodegradable particles for protein delivery. Journal of Controlled Release, 78(1-3), 15-24. doi:10.1016/s0168-3659(01)00486-2
• Mu, L., & Feng, S. (2003). A novel controlled release formulation for the anticancer drug paclitaxel (Taxol®): PLGA nanoparticles containing vitamin E TPGS. Journal of Controlled Release, 86(1), 33-48. doi:10.1016/s0168-3659(02)00320-6
• Jones, D. (2007). Cancer nanotechnology: small, but heading for the big time. Nature Reviews Drug Discovery, 6(3), 174-175. doi:10.1038/nrd2285
• Saenz Del Burgo, L., Pedraz, J., & Orive, G. (2014). Advanced nanovehicles for cancer management. Drug Discovery Today, 19(10), 1659-1670. doi:10.1016/j.drudis.2014.06.020
• Misra, R., Acharya, S., & Sahoo, S. K. (2010). Cancer nanotechnology: application of nanotechnology in cancer therapy. Drug Discovery Today, 15(19-20), 842-850. doi:10.1016/j.drudis.2010.08.006
• El-Serag, H. B. (2001). Epidemiology of Hepatocellular Carcinoma. Clinics in Liver Disease, 5(1), 87-107. doi:10.1016/s1089-3261(05)70155-0
• Garg, A., Sharma, R., Pandey, V., Patel, V., & Yadav, A. K. (2017). Heparin-Tailored Biopolymeric Nanocarriers in Site-Specific Delivery: A Systematic Review. Critical Reviews™ in Therapeutic Drug Carrier Systems, 34(1), 1-33. doi:10.1615/critrevtherdrugcarriersyst.2017016794

This work is licensed under a Creative Commons Attribution 4.0 International License.