Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells

Aeshah A Awaji; Moustafa A Rizk; Raiedhah A Alsaiari; Norah F Alqahtani; Fatima A Al-Qadri; Ali S Alkorbi; Hani S Hafez; Reda F M Elshaarawy

doi:10.3390/ph16121711

Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells

Pharmaceuticals (Basel). 2023 Dec 11;16(12):1711. doi: 10.3390/ph16121711.

Authors

Aeshah A Awaji¹, Moustafa A Rizk², Raiedhah A Alsaiari², Norah F Alqahtani³, Fatima A Al-Qadri², Ali S Alkorbi², Hani S Hafez⁴, Reda F M Elshaarawy^{5

6}

Affiliations

¹ Department of Biology, Faculty of Science, University College in Taymaa, University of Tabuk, Tabuk 71491, Saudi Arabia.
² Department of Chemistry, Faculty of Science and Arts at Sharurah, Najran University, Sharurah 68342, Saudi Arabia.
³ Department of Chemistry, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia.
⁴ Zoology Department, Faculty of Science, Suez University, Suez 43533, Egypt.
⁵ Department of Chemistry, Faculty of Science, Suez University, Suez 43533, Egypt.
⁶ Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine Universität Düsseldorf, 40204 Düsseldorf, Germany.

Abstract

Two bis-(imidazolium-vanillylidene)-(R,R)-diaminocyclohexane ligands (H₂(VAN)₂dach, H₂L_1,2) and their Pd(II) complexes (PdL₁ and PdL₂) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL₁LNP and PdL₂LNP), which are physicochemically and morphologically characterized. PdL₁LNP and PdL₂LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd_1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd_1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL₁LNP and PdL₂LNP to downregulate TGFβ1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.

Keywords: FGFR2/FGF2; HER2/neu; Pd(II) complexes-enacapsulated nanolipids; apoptosis; cytotoxicity; imidazolium–vanillylidene ligands.

Grants and funding

NU/IFC/2/SERC/-/7/Najran University