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

Authors
  • Castro, Flávia1
  • Pinto, Marta L2
  • Pereira, Catarina L3
  • Serre, Karine4
  • Barbosa, Mário A1
  • Vermaelen, Karim5
  • Gärtner, Fátima6
  • Gonçalves, Raquel M1
  • De Wever, Olivier7
  • Oliveira, Maria J8
  • 1 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. , (Portugal)
  • 2 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. , (Portugal)
  • 3 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal. , (Portugal)
  • 4 IMM - Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. , (Portugal)
  • 5 Tumor Immunology Laboratory, Department of Pulmonary Medicine and Immuno-Oncology Network Ghent, Ghent University Hospital, Ghent, Belgium; CRIG - Cancer Research Institute Ghent, Ghent University, Belgium. , (Belgium)
  • 6 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal. , (Portugal)
  • 7 CRIG - Cancer Research Institute Ghent, Ghent University, Belgium; LECR - Laboratory Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Belgium. , (Belgium)
  • 8 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. Electronic address: [email protected] , (Portugal)
Type
Published Article
Journal
Biomaterials
Publication Date
Oct 01, 2020
Volume
257
Pages
120218–120218
Identifiers
DOI: 10.1016/j.biomaterials.2020.120218
PMID: 32736253
Source
Medline
Keywords
Language
English
License
Unknown

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+IFN-γ+ 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. Copyright © 2020 Elsevier Ltd. All rights reserved.

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