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Purpose <p>Lung cancer is the second most common Cancer in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. 5-fluorouracil (5-FU) is among the most administrated chemotherapeutic agents for various neoplasms. This study focused on synthesizing and characterizing P(AAm/SA)/5-Fu nanogels as a potential drug delivery system.</p> Methods <p>The nanogels were prepared by combining sodium alginate (SA) and acrylamide (AAm) monomers, followed by gamma irradiation-induced polymerization at a dose of 5&#xa0;kGy. Then, the obtained nanogel was loaded with 500&#xa0;ppm of 5-Fu. Transmission electron microscopy (TEM) imaging was utilized to characterize the nanogels' morphology and monodispersity with a particle size of (50&#xa0;nm). Rats were randomly assigned to four groups (six animals per group): Group 1: (Control): normal healthy. Group 2: Cancer-bearing animals (animals injected with diethylnitrosamine (DEN) 20&#xa0;mg/kg body weight for 3&#xa0;months. Group 3: Cancer+ 5-fluorouracil (12&#xa0;mg/kg body weight). Group4: Cancer+ 5-Flurouracil- Loaded P (AAm/SA) Nanogel.</p> Results <p>DEN markedly increased PTGS2, Cox2, PKB, PFKm, and ERK1 levels. Also, observed up-regulation in ALKBH5, Beclin1, ULK1, and P53 gene expressions in the cancer-bearing animal group compared with the control group. 5-fluorouracil nano gel significantly ameliorated the above-mentioned parameters and immunohistochemistry study. 5-fluorouracil nanogel significantly ameliorated the parameters mentioned above, as well as the immunohistochemistry study.</p> Conclusion <p>The 5-FU-loaded P(AAm/SA) nanogel could serve as a promising approach for targeting tumor cell proliferation, speeding up autophagic processes, and overcoming chemotherapy resistance in lung carcinoma.</p>

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Targeting cell signaling pathway ALKBH5/Beclin1/ULK1 in lung cancer by 5-flurouracil- loaded P (AAm/SA) nanogel in rats

  • 期刊论文

  • 发表日期：

    2025年5月1日

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  • Ahmad S. Kodous,
  • Eman S. Eldin,
  • Hebatallah E. Mohamed,
  • Mohamed Mohamady Ghobashy,
  • Dina F. EL-Maghraby

摘要

Purpose

Lung cancer is the second most common Cancer in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. 5-fluorouracil (5-FU) is among the most administrated chemotherapeutic agents for various neoplasms. This study focused on synthesizing and characterizing P(AAm/SA)/5-Fu nanogels as a potential drug delivery system.

Methods

The nanogels were prepared by combining sodium alginate (SA) and acrylamide (AAm) monomers, followed by gamma irradiation-induced polymerization at a dose of 5 kGy. Then, the obtained nanogel was loaded with 500 ppm of 5-Fu. Transmission electron microscopy (TEM) imaging was utilized to characterize the nanogels' morphology and monodispersity with a particle size of (50 nm). Rats were randomly assigned to four groups (six animals per group): Group 1: (Control): normal healthy. Group 2: Cancer-bearing animals (animals injected with diethylnitrosamine (DEN) 20 mg/kg body weight for 3 months. Group 3: Cancer+ 5-fluorouracil (12 mg/kg body weight). Group4: Cancer+ 5-Flurouracil- Loaded P (AAm/SA) Nanogel.

Results

DEN markedly increased PTGS2, Cox2, PKB, PFKm, and ERK1 levels. Also, observed up-regulation in ALKBH5, Beclin1, ULK1, and P53 gene expressions in the cancer-bearing animal group compared with the control group. 5-fluorouracil nano gel significantly ameliorated the above-mentioned parameters and immunohistochemistry study. 5-fluorouracil nanogel significantly ameliorated the parameters mentioned above, as well as the immunohistochemistry study.

Conclusion

The 5-FU-loaded P(AAm/SA) nanogel could serve as a promising approach for targeting tumor cell proliferation, speeding up autophagic processes, and overcoming chemotherapy resistance in lung carcinoma.