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Chitosan/γ-PGA nanoparticles-based immunotherapy as adjuvant to radiotherapy in breast cancer.

Authors :
Castro F
Pinto ML
Pereira CL
Serre K
Barbosa MA
Vermaelen K
Gärtner F
Gonçalves RM
De Wever O
Oliveira MJ
Source :
Biomaterials [Biomaterials] 2020 Oct; Vol. 257, pp. 120218. Date of Electronic Publication: 2020 Jul 07.
Publication Year :
2020

Abstract

Radiotherapy (RT) is an essential treatment modality for several types of cancer. Despite its therapeutic potential, RT is frequently insufficient to overcome the immunosuppressive nature of the tumor microenvironment, failing to control tumor metastases. Innovative immunomodulatory strategies, like immunostimulatory biomaterials could be used to boost the immunogenic effects of RT. Herein, we addressed the synergistic potential of immunostimulatory chitosan/poly(γ-glutamic acid) nanoparticles (Ch/γ-PGA NPs) combined with RT to induce antitumor immunity in the 4T1 orthotopic breast tumor mouse model. Non-treated animals had progressive primary tumor growth and developed splenomegaly and lung metastases. While RT decreased primary tumor burden, Ch/γ-PGA NPs-treatment decreased systemic immunosuppression and lung metastases. The combination therapy (RT + Ch/γ-PGA NPs) synergistically impaired 4T1 tumor progression, which was associated with a significant primary tumor growth and splenomegaly reduction, a decrease in the percentage of splenic immunosuppressive myeloid cells and an increase in antitumoral CD4 <superscript>+</superscript> IFN-γ <superscript>+</superscript> population. Notably, animals from the combination therapy presented less and smaller lung metastatic foci and lower levels of the systemic pro-tumor cytokines IL-3, IL-4, IL-10, and of the CCL4 chemokine, in comparison to non-treated animals. Overall, these results evidenced that Ch/γ-PGA NPs potentiate and synergize with RT, headlining their promising role as adjuvant anticancer strategies.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1878-5905
Volume :
257
Database :
MEDLINE
Journal :
Biomaterials
Publication Type :
Academic Journal
Accession number :
32736253
Full Text :
https://doi.org/10.1016/j.biomaterials.2020.120218