Related Experiment Video
Updated: Jun 30, 2025
Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
Published on: August 18, 2010
Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer
Walison Nunes da Silva1, Pedro Augusto Carvalho Costa1, Sérgio Ricardo Aluotto Scalzo Júnior1
1Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
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.
Insights
This study developed lipid nanoparticles (LNPs) to deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA directly to tumors, enhancing cancer cell death. Combining LNP-TRAIL with tumor microenvironment normalization therapies proved effective in inhibiting colon cancer progression.
Area of Science:
- Oncology
- Immunotherapy
- Nanomedicine
Background:
- Immunotherapy offers a promising approach to cancer treatment by leveraging the immune system for enhanced antitumor responses.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a key molecule in cancer-specific therapies due to its ability to induce apoptosis in tumor cells.
Purpose of the Study:
- To develop and evaluate an ionizable lipid nanoparticle (LNP) platform for delivering TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME).
- To assess the efficacy of LNP-TRAIL in inducing tumor cell death in vitro and inhibiting colon cancer progression in vivo, particularly in combination with TME normalization strategies.
Main Methods:
- Formulation of LNP-TRAIL using microfluidic mixing.
- In vitro assessment of LNP-TRAIL-mediated tumor cell death.
- In vivo evaluation of LNP-TRAIL efficacy in a mouse model of colon cancer, with and without TME normalization using Losartan or Angiotensin 1-7.
Main Results:
- LNP-TRAIL demonstrated efficacy in inducing tumor cell death in vitro.
- In vivo studies showed that LNP-TRAIL effectively inhibited colon cancer progression.
- Combination therapy of LNP-TRAIL with TME normalization (Losartan or Angiotensin 1-7) resulted in potent tumor cell death, enhanced apoptosis, and necrosis within the tumor tissue.
Conclusions:
- The developed LNP platform is effective in delivering TRAIL mRNA to the TME, inducing tumor cell death.
- Combining LNP-TRAIL with TME normalization strategies represents a promising therapeutic approach for solid tumors.
- These findings offer valuable insights for developing novel immunotherapeutic strategies against solid tumors.
Related Concept Videos
01:22MicroRNAs
01:15Drugs that Stabilize Microtubules