Gold nanoparticles linked to a cancer drug have been shown to improve the killing of ovarian cancer cells, especially in drug-resistant cases.
Image Credit: AshTproductions/Shutterstock.com
A team of researchers has developed gold nanoparticles (AuNPs) conjugated with trastuzumab as a possible cancer treatment. Published in Cancer Nanotechnology, the study focused on how these tiny particles interact with SKOV3 ovarian cancer cells, particularly those modified to express microRNA-200c.
Gold nanoparticles are widely studied in nanomedicine due to their biocompatibility, stability, and selective binding to biological molecules like antibodies. Their optical properties make them useful not only in drug delivery but also for confirming successful conjugation through shifts in surface plasmon resonance, measured by UV-visible spectroscopy.
These engineered nanoparticles are particularly interesting as a strategy to overcome trastuzumab resistance in HER2-positive ovarian cancer, an area where current treatments often fall short.
Optimising Size, Loading, and Release
Under 10 nanometres in diameter, the AuNPs were functionalized with thiol groups and loaded with trastuzumab (TZ). The research team then tested their impact on SKOV3 ovarian cancer cells, with and without overexpression of microRNA-200c (miR-200c).
miR-200c is known for inhibiting the epithelial-mesenchymal transition (EMT); however, its ability to modulate HER2 signalling and improve trastuzumab sensitivity had not previously been studied in this context.
The researchers tested two antibody-to-nanoparticle weight ratios (1:2 and 1:1) and found the 1:1 ratio to provide the highest loading efficiency at 41 %. The observed conjugation was likely achieved through noncovalent interactions, supported by the gradual release of antibody observed over time.
Characterization using dynamic light scattering showed an increase in hydrodynamic diameter from a few nanometres to over 200 nm, indicating successful binding and possible aggregation. Field emission scanning electron microscopy confirmed a mostly well-dispersed population, with some larger clusters attributed to drying effects during sample prep.
UV-vis spectroscopy also showed clear spectral shifts after conjugation, reflecting decreased interparticle spacing and further validating successful antibody attachment.
Sustained Release and Biological Activity
The stability and antibody release profile of the AuNPs were evaluated over 48 hours at 37 °C. Approximately 40 to 60 % of the bound antibody was released during this period, highlighting the potential for a controlled, sustained therapeutic effect in vivo.
For biological testing, both parental and microRNA-200c-transfected SKOV3 cells were exposed to the conjugates at 0.1, 0.5, and 1 μg/ml for 24, 48, and 72 hours. MTT assays showed reduced cell viability at higher doses and longer exposure times, with the most potent effects observed in microRNA-200c-expressing cells.
Triggering Apoptosis And Disrupting Signalling
Flow cytometry using Annexin V and 7-AAD staining confirmed increased apoptosis in treated cells, particularly at the 1 μg/ml dose. Both early and late apoptotic populations were elevated, indicating that the conjugates effectively triggered programmed cell death.
Western blot analysis provided further insight into the mechanism at play. After treatment, levels of phosphorylated HER2, KRAS, and p-MAPK were all reduced, suggesting the conjugates disrupt the HER2-MAPK signalling axis, critical for cancer cell survival and proliferation. Total HER2 levels remained relatively unchanged, pointing to specific inhibition of activation rather than receptor loss.
Toward Smarter Delivery Systems
This work demonstrates that AuNP-trastuzumab conjugates not only bind and release the antibody in a stable, controlled manner, but also deliver clear biological effects in vitro. By downregulating key oncogenic pathways and enhancing apoptosis in sensitive ovarian cancer cells, they show potential as a precision therapy, especially in cases where microRNA-200c expression is high.
Further research is still needed to evaluate in vivo behaviour, biodistribution, and therapeutic efficacy. Still, these results offer a promising foundation for improving targeted cancer treatment with such nanoparticle-based systems.
Journal Reference
Salamone T.A., et al. (2025). MiR-200c synergizes with trastuzumab-loaded gold nanoparticles to overcome resistance in ovarian cancer cells. Cancer Nanotechnology 16, 29. DOI: 10.1186/s12645-025-00330-5, https://cancer-nano.biomedcentral.com/articles/10.1186/s12645-025-00330-5