Antitumor activity of 5-fluorouracil polymeric nanogel synthesized by gamma radiation on a rat model of colon carcinoma: a proposed mechanism

The use of 5-fluorouracil (5-FU) is associated with multifaceted challenges and poor pharmacokinetics. Accordingly, our study was designed to prepare 5-FU nanogel as a new form of the colon cancer chemotherapeutic drug 5-FU using polyacrylic acid and gelatin hybrid nanogel as efficient drug carriers...

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Published in:Discover. Oncology 2023-07, Vol.14 (1), p.138-138, Article 138
Main Authors: Abo-Zaid, Omayma A. R., Moawed, Fatma S. M., Barakat, Wael E. M., Ghobashy, Mohamed Mohamady, Ahmed, Esraa S. A.
Format: Article
Language:English
Subjects:
5-fluorouracil nanogel
Autophagy
Biodegradation
Brief Communication
Cancer Research
Cancer therapies
Colon cancer
Colorectal cancer
Cytotoxicity
Drug delivery systems
Drug dosages
Hydrogels
Internal Medicine
Medicine
Medicine & Public Health
Molecular Medicine
Nanoparticles
NF-κβ
Oncology
Particle size
PI3K
Polymers
Radiation
Radiotherapy
Surgical Oncology
TLR2
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Summary:The use of 5-fluorouracil (5-FU) is associated with multifaceted challenges and poor pharmacokinetics. Accordingly, our study was designed to prepare 5-FU nanogel as a new form of the colon cancer chemotherapeutic drug 5-FU using polyacrylic acid and gelatin hybrid nanogel as efficient drug carriers. Alongside the in vivo chemotherapeutic evaluation, the anti-proliferative and anti-apoptotic efficacy were carried out for 5-FU nanogel against 1,2-dimethylhydrazine (DMH, 20 mg/kg) and γ-radiation (4 Gy)-prompted colon dysplasia in rats compared to 5-FU. The morphology and size of 5-FU nanogel were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) in addition to cytotoxicity assay. The expression of phosphoinositide-3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR); Toll-like receptor2 (TLR2)/nuclear factor kappa B), adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream autophagy-related genes in addition to apoptotic markers were measured in colon tissues. Results: 5-FU nanogel reduced the levels of the TLR2/ NF-κβ as well as the expression of PI3K/AKT/mTOR. Moreover, it promoted autophagy through the activation of the AMPK and its downstream targets which consequently augmented the intrinsic and extrinsic apoptotic pathways. Conclusion: Collectively, these data might strengthen the therapeutic potential of 5-FU nanogel which can be used as an antitumor product for colon cancer.
ISSN:2730-6011
2730-6011
DOI:10.1007/s12672-023-00733-z