Antitumor activity and targeting p53-PUMA mRNA expression by 5-flurouracil PLGA-lipid polymeric nanoparticles in mouse mammary carcinomas: comparison to free 5-flurouracil

Abstract

Polymeric poly (lactic-co-glycolic acid) (PLGA)-lipid hybrid nanoparticles (PNPs)-based therapy are powerful carriers for various therapeutic agents. This study was conducted to evaluate the chemotherapeutic potential of free 5-flurouracil (5FU) and synthetized 5FU-PNPs and impact on p53-dependent apoptosis in mammary carcinomas (MCs) grown in mice. Breast cancer cells were injected in Swiss albino female mice and 2 bilateral masses of MC were confirmed after one week. Mice were distributed to five experimental groups; Group 1: MC control group. Groups 2 and 3: MC + free 5FU [5 or 10 mg per kg] groups. Groups 4 and 5: synthetized MC+ 5FU-PNPs [5 or 10 mg per kg] groups. Medications were administered orally, twice weekly for 3 weeks. Then, tumors were dissected, and sections were stained with hematoxylin-eosin (HE) while the other MC was used for measuring of cell death and inflammatory markers. Treatment with 5FU-PNPs suppressed the MC masses and pathologic scores based on HE-staining. Similarly, greater proapoptotic activity was recorded in 5FU-PNPs groups compared to free 5FU groups as shown by significant upregulation in tumoral p53 immunostaining. The current results encourage the utility of PNPs for improving the antitumor effect of 5FU. The chemotherapeutic potential was mediated through enhancement of tumoral p53-mediated p53 up-regulated modulator of apoptosis (PUMA) genes. Additional studies are warranted for testing the antitumor activity of this preparation in other mouse models of breast cancer.

Keywords:

• Apoptosis
• 5-flurouracil
• mouse mammary carcinoma
• PLGA polymeric nanoparticles
• p53-mediated PUMA

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research at the University of Tabuk for funding this work through research no. S-1443-0075.

Author contributions

Conceptualization, Ahmed Gardouh, Hebatallah Atteia, and Sawsan Zaitone; Data curation, Mohamed F. Mandour, and Hatem Mokhtar;

Formal analysis, Mohamed F. Mandour and Hatem Mokhtar;

Funding acquisition, and Sawsan Zaitone;

Investigation, Sara Alsharif, Zood Alaqais, Lama Alharbi, Maha Almarwani, Fatma Azzahraa Hisham, Ghena Mohammed, and Eman M. Shorog;

Methodology, Ahmed Gardouh, Hatem Mokhtar, Zood Alaqais, Fatma Azzahraa Hisham, Mohamed Abdellah, Hebatallah Atteia and Sawsan Zaitone;

Project administration, Hebatallah Atteia, and Sawsan Zaitone;

Resources, Ahmed Gardouh, Hatem Mokhtar, Zood Alaqais, Fatma Azzahraa Hisham, Mohamed Abdellah, Ghena Mohammed, and Abdulrahman Almaeen;

Software, Sara Alsharif, Mohamed F. Mandour, Hatem Mokhtar, Zood Alaqais, Lama Alharbi, Maha Almarwani, and Fatma Azzahraa Hisham;

Validation, Eman M. Shorog, and Hebatallah Atteia;

Visualization, Sara Alsharif, Mohamed F. Mandour, Zood Alaqais, Lama Alharbi, Maha Almarwani, Fatma Azzahraa Hisham, Ghena Mohammed, Eman M. Shorog, Abdulrahman Almaeen, and Hebatallah Atteia;

Writing – original draft, Ahmed Gardouh, Mohamed F. Mandour, Hatem Mokhtar, Zood Alaqais, Lama Alharbi, and Fatma Azzahraa Hisham;

Writing – review and editing, Mohamed F. Mandour, Hatem Mokhtar, Mohamed Abdellah, Ghena Mohammed, Eman M. Shorog, Abdulrahman Almaeen, Hebatallah Atteia, and Sawsan Zaitone.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data are available from the authors upon request.

Additional information

Funding

The authors received funding from the Deanship of Scientific Research at the University of Tabuk through research no. S-1443-0075.