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

Autor:	da Silva WN; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Carvalho Costa PA; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Scalzo Júnior SRA; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Ferreira HAS; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Prazeres PHDM; Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil., Campos CLV; Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil., Rodrigues Alves MT; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Alves da Silva NJ; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., de Castro Santos AL; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Guimarães LC; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Chen Ferris ME; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Thatte A; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Hamilton A; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Bicalho KA; Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil., Lobo AO; Department of Materials Engineering, Federal University of Piauí, Teresina, PI, Brazil., Santiago HDC; Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil., da Silva Barcelos L; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Figueiredo MM; State University of Minas Gerais, Divinopolis, MG, Brazil., Teixeira MM; Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil., Vasconcelos Costa V; Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Mitchell MJ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Frézard F; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil., Pires Goulart Guimaraes P; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Jazyk:	angličtina
Zdroj:	International journal of nanomedicine [Int J Nanomedicine] 2024 Mar 14; Vol. 19, pp. 2655-2673. Date of Electronic Publication: 2024 Mar 14 (Print Publication: 2024).
DOI:	10.2147/IJN.S452896
Abstrakt:	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. Competing Interests: The authors declare that they have no conflicts of interest in this work. (© 2024 da Silva et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu