Details

Autor(en) / Beteiligte

• da Silva, Walison Nunes
• Carvalho Costa, Pedro Augusto
• Scalzo Júnior, Sérgio Ricardo Aluotto
• Ferreira, Heloísa A S
• Prazeres, Pedro Henrique Dias Moura
• Campos, Caroline Leonel Vasconcelos
• Rodrigues Alves, Marco Túllio
• Alves da Silva, Natália Jordana
• de Castro Santos, Ana Luiza
• Guimarães, Lays Cordeiro
• Chen Ferris, Maria Eduarda
• Thatte, Ajay
• Hamilton, Alex
• Bicalho, Kelly Alves
• Lobo, Anderson Oliveira
• Santiago, Helton da Costa
• da Silva Barcelos, Lucíola
• Figueiredo, Maria Marta
• Teixeira, Mauro Martins
• Vasconcelos Costa, Vivian
• Mitchell, Michael J
• Frézard, Frédéric
• Pires Goulart Guimaraes, Pedro

Titel

Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression

Ist Teil von

• International journal of nanomedicine, 2024-01, Vol.19, p.2655-2673

Ort / Verlag

New Zealand: Dove Medical Press Limited

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.