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Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages
Megan A Mackey1, Farhat Saira, Mahmoud A Mahmoud
1Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States.
Abstract:
Recently, we have shown that targeting the cancer cell nucleus with solid gold nanospheres, using a cancer cell penetrating/pro-apoptotic peptide (RGD) and a nuclear localization sequence peptide (NLS), inhibits cell division, thus leading to apoptosis. In the present work, flow cytometric analysis revealed an increase in cell death, via apoptosis and necrosis, in HSC cells upon treatment with peptide-conjugated hollow gold nanocages, compared to those treated with the peptide-conjugated solid gold nanospheres. This is consistent with a G0/G1 phase accumulation, S phase depletion, and G2/M phase depletion, as well as reduced ATP levels. Here, we investigate the possible causes for the observed enhanced cell death with the use of confocal microscopy. The fluorescence images of HSC cells treated with gold nanocages indicate the presence of reactive oxygen species, known to cause apoptosis. The formation of reactive oxygen species observed is consistent with a mechanism involving the oxidation of metallic silver on the inner cavity of the nanocage (inherent to the synthesis of the gold nanocages) to silver oxide. This oxidation is confirmed by an observed redshift in the surface plasmon resonance of the gold nanocages in cell culture medium. The silver oxide, a semiconductor known to photochemically generate hydroxyl radicals, a form of reactive oxygen species, is proposed as a mechanism for the enhanced cell death caused by gold nanocages. Thus, the enhanced cell death, via apoptosis and necrosis, observed with peptide-conjugated hollow gold nanocage-treated cells is considered to be a result of the metallic composition (silver remaining on the inner cavity) of the nanocage.
Insights
Hollow gold nanocages conjugated with peptides enhance cancer cell death through apoptosis and necrosis. This effect is attributed to silver oxide formation within the nanocages, generating reactive oxygen species.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Previous studies demonstrated solid gold nanospheres conjugated with RGD and NLS peptides induce apoptosis by inhibiting cancer cell division.
- Hollow gold nanocages offer potential for enhanced therapeutic delivery and efficacy compared to solid nanoparticles.
Purpose of the Study:
- To investigate the enhanced cell death observed in HSC cells treated with peptide-conjugated hollow gold nanocages compared to solid gold nanospheres.
- To elucidate the underlying mechanisms responsible for the increased apoptosis and necrosis induced by hollow gold nanocages.
Main Methods:
- Flow cytometry was used to analyze cell death (apoptosis and necrosis) and cell cycle progression (G0/G1, S, G2/M phases).
- Confocal microscopy was employed to visualize reactive oxygen species (ROS) generation within treated cells.
- Surface plasmon resonance (SPR) was measured to confirm chemical changes in the nanocages.
Main Results:
- Peptide-conjugated hollow gold nanocages significantly increased apoptosis and necrosis in HSC cells compared to solid gold nanospheres.
- Hollow gold nanocage treatment led to G0/G1 phase arrest, S and G2/M phase depletion, and reduced ATP levels.
- Confocal microscopy revealed increased ROS production in cells treated with hollow gold nanocages, linked to silver oxidation to silver oxide.
Conclusions:
- The enhanced cell death induced by peptide-conjugated hollow gold nanocages is primarily due to the generation of reactive oxygen species from the silver oxide component within the nanocage cavity.
- The metallic composition of the hollow gold nanocages, specifically the silver oxide, plays a crucial role in their enhanced anticancer efficacy.
- These findings suggest hollow gold nanocages are a promising platform for cancer therapy, offering improved cell death induction via ROS generation.
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