Author | Silva, Walison Nunes da | |
Author | Costa, Pedro Augusto Carvalho | |
Author | Scalzo Júnior, Sérgio Ricardo Aluotto | |
Author | Ferreira, Heloísa A S | |
Author | Prazeres, Pedro Henrique Dias Moura | |
Author | Campos, Caroline Leonel Vasconcelos | |
Author | Alves, Marco Túllio Rodrigues | |
Author | Silva, Natália Jordana Alves da | |
Author | Santos, Ana Luiza de Castro | |
Author | Guimarães, Lays Cordeiro | |
Author | Ferris, Maria Eduarda Chen | |
Author | Thatte, Ajay | |
Author | Hamilton, Alex | |
Author | Bicalho, Kelly Alves | |
Author | Lobo, Anderson Oliveira | |
Author | Santiago, Helton da Costa | |
Author | Barcelos, Lucíola da Silva | |
Author | Figueiredo, Maria Marta | |
Author | Teixeira, Mauro Martins | |
Author | Costa, Vivian Vasconcelos | |
Author | Mitchell, Michael J | |
Author | Frézard, Frédéric | |
Author | Guimaraes, Pedro Pires Goulart | |
Access date | 2024-04-17T18:31:25Z | |
Available date | 2024-04-17T18:31:25Z | |
Document date | 2024 | |
Citation | DA SILVA, Walison Nunes et al. Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression. Int J Nanomedicine, v. 19, p. 2655-2673, 2024. ISSN 1178-2013. doi.org/10.2147/IJN.S452896. | en_US |
ISSN | 1176-9114 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/63529 | |
Language | eng | en_US |
Publisher | DOVE Medical Press | en_US |
Rights | open access | en_US |
Title | Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression | en_US |
Type | Article | en_US |
Abstract | Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention.
Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice.
Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization.
Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Pathology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA. | en_US |
Affilliation | Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Materials Engineering. Federal University of Piauí. Teresina, PI, Brazil. | en_US |
Affilliation | Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | State University of Minas Gerais. Divinopolis, MG, Brazil. | en_US |
Affilliation | Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Subject | TRAIL | en_US |
Subject | angiotensin (1–7) | en_US |
Subject | immunotherapy | en_US |
Subject | lipid nanoparticle | en_US |
Subject | losartan | en_US |
Subject | mRNA | en_US |