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https://www.arca.fiocruz.br/handle/icict/63529
IONIZABLE LIPID NANOPARTICLE-MEDIATED TRAIL MRNA DELIVERY IN THE TUMOR MICROENVIRONMENT TO INHIBIT COLON CANCER PROGRESSION
Author
Silva, Walison Nunes da
Costa, Pedro Augusto Carvalho
Scalzo Júnior, Sérgio Ricardo Aluotto
Ferreira, Heloísa A S
Prazeres, Pedro Henrique Dias Moura
Campos, Caroline Leonel Vasconcelos
Alves, Marco Túllio Rodrigues
Silva, Natália Jordana Alves da
Santos, Ana Luiza de Castro
Guimarães, Lays Cordeiro
Ferris, Maria Eduarda Chen
Thatte, Ajay
Hamilton, Alex
Bicalho, Kelly Alves
Lobo, Anderson Oliveira
Santiago, Helton da Costa
Barcelos, Lucíola da Silva
Figueiredo, Maria Marta
Teixeira, Mauro Martins
Costa, Vivian Vasconcelos
Mitchell, Michael J
Frézard, Frédéric
Guimaraes, Pedro Pires Goulart
Costa, Pedro Augusto Carvalho
Scalzo Júnior, Sérgio Ricardo Aluotto
Ferreira, Heloísa A S
Prazeres, Pedro Henrique Dias Moura
Campos, Caroline Leonel Vasconcelos
Alves, Marco Túllio Rodrigues
Silva, Natália Jordana Alves da
Santos, Ana Luiza de Castro
Guimarães, Lays Cordeiro
Ferris, Maria Eduarda Chen
Thatte, Ajay
Hamilton, Alex
Bicalho, Kelly Alves
Lobo, Anderson Oliveira
Santiago, Helton da Costa
Barcelos, Lucíola da Silva
Figueiredo, Maria Marta
Teixeira, Mauro Martins
Costa, Vivian Vasconcelos
Mitchell, Michael J
Frézard, Frédéric
Guimaraes, Pedro Pires Goulart
Affilliation
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Pathology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Department of Materials Engineering. Federal University of Piauí. Teresina, PI, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
State University of Minas Gerais. Divinopolis, MG, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Pathology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Department of Materials Engineering. Federal University of Piauí. Teresina, PI, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
State University of Minas Gerais. Divinopolis, MG, Brazil.
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Morphology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Bioengineering. University of Pennsylvania. Philadelphia, PA, USA.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
Department of Physiology and Biophysics. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil.
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.
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