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Updated: Apr 16, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
RNA-based TWIST1 inhibition via dendrimer complex to reduce breast cancer cell metastasis
James Finlay1, Cai M Roberts2, Gina Lowe3
1Department of Neurosciences, City of Hope Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA ; Irell & Manella Graduate School of Biological Sciences, City of Hope Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA ; Division of Comparative Medicine, City of Hope Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA.
Abstract:
Breast cancer is the leading cause of cancer-related deaths among women in the United States, and survival rates are lower for patients with metastases and/or triple-negative breast cancer (TNBC; ER, PR, and Her2 negative). Understanding the mechanisms of cancer metastasis is therefore crucial to identify new therapeutic targets and develop novel treatments to improve patient outcomes. A potential target is the TWIST1 transcription factor, which is often overexpressed in aggressive breast cancers and is a master regulator of cellular migration through epithelial-mesenchymal transition (EMT). Here, we demonstrate an siRNA-based TWIST1 silencing approach with delivery using a modified poly(amidoamine) (PAMAM) dendrimer. Our results demonstrate that SUM1315 TNBC cells efficiently take up PAMAM-siRNA complexes, leading to significant knockdown of TWIST1 and EMT-related target genes. Knockdown lasts up to one week after transfection and leads to a reduction in migration and invasion, as determined by wound healing and transwell assays. Furthermore, we demonstrate that PAMAM dendrimers can deliver siRNA to xenograft orthotopic tumors and siRNA remains in the tumor for at least four hours after treatment. These results suggest that further development of dendrimer-based delivery of siRNA for TWIST1 silencing may lead to a valuable adjunctive therapy for patients with TNBC.
Insights
This study shows that a modified dendrimer can deliver siRNA to silence TWIST1 in triple-negative breast cancer (TNBC) cells, reducing their migration and invasion. This offers a potential new therapy for aggressive breast cancers.
Area of Science:
- Oncology
- Nanomedicine
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) has poor survival rates, necessitating new therapeutic strategies.
- TWIST1, a transcription factor, drives metastasis via epithelial-mesenchymal transition (EMT) and is a target for aggressive cancers.
- Poly(amidoamine) (PAMAM) dendrimers offer potential for targeted siRNA delivery.
Purpose of the Study:
- To investigate the efficacy of PAMAM dendrimer-mediated siRNA delivery for TWIST1 silencing in TNBC.
- To evaluate the impact of TWIST1 knockdown on TNBC cell migration and invasion.
- To assess the in vivo delivery and retention of siRNA in TNBC xenografts.
Main Methods:
- Utilized modified PAMAM dendrimers for complexing siRNA targeting TWIST1.
- Transfected SUM1315 TNBC cells and assessed TWIST1 and EMT gene knockdown.
- Performed wound healing and transwell assays to measure cell migration and invasion.
- Evaluated siRNA delivery and retention in orthotopic TNBC xenografts in vivo.
Main Results:
- PAMAM-siRNA complexes were efficiently internalized by TNBC cells, achieving significant TWIST1 and EMT gene knockdown.
- TWIST1 silencing persisted for up to one week, reducing cell migration and invasion.
- PAMAM dendrimers successfully delivered siRNA to xenograft tumors, with sustained presence for at least four hours.
Conclusions:
- Dendrimer-based delivery of siRNA targeting TWIST1 is effective in reducing TNBC cell migration and invasion.
- PAMAM dendrimers demonstrate potential for in vivo siRNA delivery to breast tumors.
- This approach may represent a promising adjunctive therapy for TNBC patients.
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