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Multifunctional calcium-based nanocarriers for synergistic treatment of triple-negative breast cancer
Sara A Martins1, Rui R Costa1, Alexandra Brito1
13B's Research Group, I3Bs - Research Institute On Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence On Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, 4805-017, Barco Guimarães, Portugal; ICVS/3Bs - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Abstract:
Targeted breast cancer therapies hold the potential to improve the efficiency of drug delivery to the pathology site without impacting the viability and function of healthy cells. Herein, we developed multifunctional nanocarriers that target simultaneously several downstream signaling processes in triple negative breast cancer cells. The system comprises pH sensitive CaCO3 nanoparticles (NPs) as carriers of the anticancer drug doxorubicin (DOX). The NPs were coated in a layer-by-layer (LbL) fashion using poly-l-lysine and hyaluronic acid to target receptors overexpressed in breast cancer (e.g. CD44, RHAMM). Spheroids of the triple-negative Hs578T cell line were used as a 3D model to assess the therapeutic potential of this system. Our results showed that the NPs act via a synergistic mechanism that combines Ca2+ overload causing cell calcification and DNA damage by DOX. The LbL coating was crucial for the protection of the healthy cells, i.e. it provides NPs with targeting capacity. The overall data suggests that the LbL-coated NPs loaded with DOX hold great potential for the treatment of breast cancer.
Insights
Multifunctional nanocarriers deliver the anticancer drug doxorubicin (DOX) to triple-negative breast cancer cells. This targeted approach combines drug action with calcium overload for enhanced therapeutic potential.
Area of Science:
- Nanotechnology
- Materials Science
- Oncology
Background:
- Targeted drug delivery aims to enhance cancer treatment efficacy while minimizing side effects on healthy tissues.
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to its aggressive nature and lack of targeted treatment options.
- Developing multifunctional nanocarriers is crucial for overcoming drug resistance and improving treatment outcomes.
Purpose of the Study:
- To engineer multifunctional nanocarriers for targeted delivery of doxorubicin (DOX) to triple-negative breast cancer cells.
- To investigate the synergistic therapeutic effects of combined chemotherapy and calcium overload.
- To evaluate the efficacy and safety of layer-by-layer (LbL) coated nanoparticles in a 3D cell model.
Main Methods:
- Fabrication of pH-sensitive calcium carbonate (CaCO3) nanoparticles loaded with doxorubicin (DOX).
- Layer-by-layer (LbL) coating of nanoparticles with poly-L-lysine and hyaluronic acid for targeted delivery.
- Assessment of nanoparticle efficacy and mechanism of action using 3D spheroids of the Hs578T triple-negative breast cancer cell line.
Main Results:
- The developed nanocarriers demonstrated effective targeting of triple-negative breast cancer cells in a 3D spheroid model.
- A synergistic therapeutic effect was observed, combining doxorubicin-induced DNA damage with calcium overload leading to cell calcification.
- The LbL coating provided crucial protection to healthy cells and enhanced the targeting capacity of the nanoparticles.
Conclusions:
- LbL-coated, doxorubicin-loaded CaCO3 nanoparticles show significant potential as a targeted therapy for triple-negative breast cancer.
- The dual mechanism of action (chemotherapy and calcification) offers a promising strategy for overcoming treatment resistance.
- This nanotechnology-based approach warrants further investigation for clinical translation in breast cancer treatment.
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