2. Academic Validation
  3. Multifunctional calcium-based nanocarriers for synergistic treatment of triple-negative breast cancer

Multifunctional calcium-based nanocarriers for synergistic treatment of triple-negative breast cancer

  • J Colloid Interface Sci. 2024 Jun 23:674:500-512. doi: 10.1016/j.jcis.2024.06.159.
Sara A Martins 1,  Rui R Costa 2,  Alexandra Brito 3,  Rui L Reis 4,  Natália M Alves 5,  Iva Pashkuleva 6,  Diana Soares da Costa 7
Affiliations

Affiliations

  • 1 3B'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. Electronic address: a88355@alunos.uminho.pt.
  • 2 3B'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. Electronic address: rui.costa@i3bs.uminho.pt.
  • 3 3B'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. Electronic address: alexandra.brito@i3bs.uminho.pt.
  • 4 3B'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. Electronic address: rgreis@i3bs.uminho.pt.
  • 5 3B'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. Electronic address: nalves@i3bs.uminho.pt.
  • 6 3B'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. Electronic address: pashkuleva@i3bs.uminho.pt.
  • 7 3B'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. Electronic address: diana.costa@i3bs.uminho.pt.
PMID: 38943911 DOI: 10.1016/j.jcis.2024.06.159
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.

Keywords

Breast cancer; Calcium overload; Cell spheroids; Core/shell nanoparticles; Doxorubicin; Hyaluronic acid.

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