Insights into the Cellular Uptake, Cytotoxicity, and Cellular Death Modality of Phospholipid-Coated Gold Nanorods toward Breast Cancer Cell Lines

Abstract

Gold nanorods (GNRs) have gained pronounced recognition in the diagnosis and treatment of cancers driven by their distinctive properties. Herein, a gold-based nanosystem was prepared by utilizing a phospholipid moiety linked to thiolated polyethylene glycol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG-SH, as a surface decorating agent. The synthesized phospholipid-PEG-GNRs displayed good colloidal stability upon exposure to the tissue culture medium. Cytotoxicity of phospholipid-PEG-GNRs was investigated toward MCF-7 and T47D breast cancer cells using sulforhodamine B test. The results revealed that phospholipid-PEG-GNRs demonstrated high cytotoxicity to MCF-7 cells compared to T47D cells, and minimal cytotoxicity to human dermal fibroblasts. The cellular uptake studies performed by imaging and quantitative analysis demonstrated massive internalization of phospholipid-coated GNRs into MCF-7 cells in comparison to T47D cells. The cellular death modality of cancer cells after treatment with phospholipid-PEG-GNRs was evaluated using mitochondrial membrane potential assay (JC-1 dye), gene expression analysis, and flow cytometry study. The overall results suggest that phospholipid-modified GNRs enhanced mainly the cellular apoptotic events in MCF-7 cells in addition to necrosis, whereas cellular necrosis and suppression of cellular invasion contributed to the cellular death modality in the T47D cell line upon treatment with phospholipid-PEG-GNRs. The phospholipid-coated GNRs interact in a different manner with breast cancer cell lines and could be considered for breast cancer treatment.

The Effect of Surface-Modified Gold Nanorods on the Early Stage of Embryonic Development and Angiogenesis: Insight into the Molecular Pathways

“…These genes interact with other regulatory factors such as the p53 family and regulate the apoptotic pathways [52]. These results are in line with our previous study, which demonstrated that GNR (A) significantly upregulated the expression of TP53BP2 in the MCF-7 breast cancer cell line and modulated the expression of other regulatory genes involved in several apoptotic pathways [25].…”

“…The anti-angiogenic effect of GNR in this study strongly supports their proposed anti-cancer activity towards breast cancer cell lines reported in previously published studies [24,25]. It is worth mentioning that although GNR (A) showed a significant anti-angiogenesis effect and high mortality rate toward embryos, their anti-cancer activity against breast cancer cells was observed even at concentrations much lower than that utilized in the current angiogenesis and embryogenesis studies [24,25].…”

“…We demonstrated in our previous work the cytotoxicity of GNR decorated with a phospholipid moiety (GNR (A)) towards a panel of breast cancer cell lines and their modulation effect on several regulatory factors involved in cellular apoptosis and energy metabolism [24][25][26]. Furthermore, GNR-decorated with a cholesterol moiety (GNR (B)) were utilized as an efficient nanocarrier for several drugs with relatively low cytotoxicity towards normal healthy cells [27,28,37].…”

“…Interestingly, GNR decorated with a phospholipid moiety, GNR (A), significantly retarded the formation of new blood vessels compared to GNR modified with a cholesterol ligand, GNR (B), particularly in terms of vessel junctions and vessels area. Such difference might be related to the nanorods' cellular uptake; we recently reported that coating the nanorods with a phospholipid ligand has dramatically enhanced their cellular internalization into breast cancer cells [25] and Doxorubicin-resistant breast cancer cells (unpublished work). Although the uptake of GNR into the normal fibroblasts was not significant in our previous study, these results could not be conclusive on the in-vivo studies.…”

“…Previous reports indicate that biological responses towards GNP, including cytotoxicity, cellular internalization, and bio-distribution, are strongly correlated with GNP's shape, size, and surface chemistry [21,22]. Our recent work displayed that the interaction of gold nanorods (GNR) with human skin or cancerous cells is considerably correlated with the nanoparticles' surface modification; GNR conjugated with polyethylene glycol (PEG)-phospholipid moiety exhibited enhanced uptake into human skin tissue [23] and breast cancer cell lines, promoting several apoptotic pathways [24,25], and modulating the production of metabolites responsible for cellular energy metabolism [26]. On the other hand, GNR conjugated with a cholesterol moiety was successfully utilized as a nanocarrier to deliver anti-cancer and antifungal agents [27,28].…”