. 2021 Mar;27(2):251-265.

doi: 10.1111/odi.13551. Epub 2020 Aug 6.

Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis

Marwa M Essawy^{1

2}, Sahar M El-Sheikh¹, Hanaa S Raslan¹, Heba S Ramadan³, Bin Kang⁴, Iman M Talaat^{5

6}, Marwa M Afifi^{1

7}

Affiliations

¹ Department of Oral Pathology, Faculty of Dentistry, Alexandria University, Egypt.
² Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Egypt.
³ Medical Biophysics Department, Medical Research Institute, Alexandria University, Egypt.
⁴ Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
⁵ Clinical Sciences Department, College of Medicine, University of Sharjah, UAE.
⁶ Pathology Department, Faculty of Medicine, Alexandria University, Egypt.
⁷ Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

PMID: 32657515
DOI: 10.1111/odi.13551

Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis

Marwa M Essawy et al. Oral Dis. 2021 Mar.

. 2021 Mar;27(2):251-265.

doi: 10.1111/odi.13551. Epub 2020 Aug 6.

Authors

Marwa M Essawy^{1

2}, Sahar M El-Sheikh¹, Hanaa S Raslan¹, Heba S Ramadan³, Bin Kang⁴, Iman M Talaat^{5

6}, Marwa M Afifi^{1

7}

Affiliations

¹ Department of Oral Pathology, Faculty of Dentistry, Alexandria University, Egypt.
² Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Egypt.
³ Medical Biophysics Department, Medical Research Institute, Alexandria University, Egypt.
⁴ Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
⁵ Clinical Sciences Department, College of Medicine, University of Sharjah, UAE.
⁶ Pathology Department, Faculty of Medicine, Alexandria University, Egypt.
⁷ Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

PMID: 32657515
DOI: 10.1111/odi.13551

Abstract

Objectives: Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH-sensitive and pH-resistant linkers.

Materials and methods: We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH-sensitive and pH-resistant DOX bioconjugates in hamster buccal pouch carcinoma model.

Results: Our data indicate that pH-resistant and pH-sensitive DOX-nanoconjugates were equally localized in cancer cells, but the pH-resistant DOX nanoparticles were more localized in the nuclei inducing a 2-fold increase in the apoptotic effect compared with the pH-sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH-resistant AuNPs compared with pH-sensitive ones.

Conclusion: Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH-resistant AuNPs enhanced accumulation of AuNPs in cancer cells' nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.

Keywords: apoptosis; doxorubicin; gold nanoparticles; hamster buccal pouch carcinoma; oral squamous cell carcinoma.

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Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis

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Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis

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