Portal de investigación
Folate- and aCD47-functionalized lipid nanoparticles efficiently deliver mRNA and remodel pancreatic tumor microenvironment
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Parés M.
- Martínez-Latorre J.
- Candela-Noguera V.
- Pallaruelo-Santamaría V.
- Fillat C.
Grupos
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and treatment-resistant malignancies, with limited efficacy to conventional treatments such as surgical resection or chemotherapy. This clinical scenario underscores the need for novel therapeutic strategies. The development of multifunctional platforms capable of targeting tumors through multiple mechanisms offers an innovative strategy to overcome this challenge. Lipid nanoparticles (LNPs) offer a versatile platform capable of efficiently delivering genetic material. Moreover, through surface functionalization it is feasible to improve LNP performance optimizing therapeutic outcomes in a single formulation. Here, we explored a dual functionalization strategy of the LNP for tumor targeting and tumor remodeling to improve treatment efficacy. LNPs were designed for delivering reporter DNA plasmid or mRNA into the PDAC cellular models Capan-2 and PANC-1. The DNA plasmid contains a pancreatic cancer-specific chimeric promoter for transcriptional specificity to PDAC cells. Besides, LNPs were functionalized with folate and an anti-CD47 antibody to both target the folate receptor in PDAC cells and block CD47-mediated immune evasion. Both pDNA and mRNA LNPs targeted PDAC cells in a dose-dependent manner, with mRNA-LNPs demonstrating more efficient transfection. Notably, LNPs functionalized with the anti-CD47 antibody increased phagocytosis in vitro , and promoted an inflammatory phenotype of M1-like macrophages in mouse Capan-2 xenografts. This combinatorial design of the formulated LNP represents an innovative therapeutic strategy and opens future perspectives in the search for effective treatments for PDAC. © 2025 The Authors.
Datos de la publicación
- ISSN/ISSNe:
- 0753-3322, 1950-6007
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 41496333
- Enlace a otro recurso:
- www.scopus.com
- Factor de Impacto:
- 1,194 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
BIOMEDICINE & PHARMACOTHERAPY ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
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- No hay documentos
Filiaciones
Keywords
- Animals; Carcinoma, Pancreatic Ductal; CD47 Antigen; Cell Line, Tumor; Folic Acid; Humans; Lipids; Liposomes; Mice; Nanoparticles; Pancreatic Neoplasms; RNA, Messenger; Tumor Microenvironment; antibody; CD47 antibody; folate receptor; folic acid; lipid nanoparticle; messenger RNA; nanocarrier; plasmid DNA; unclassified drug; CD47 antigen; folic acid; lipid; Lipid Nanoparticles; liposome; messenger RNA; nanoparticle; animal experiment; animal model; animal tissue; Article; Capan-2 cell line; carcinoma cell; controlled study; dose response; drug efficacy; drug targeting; female; gene delivery system; genetic transfection; human; human cell; in vitro study; M1 tumor-associated macrophage; mouse; nonhuman; PANC-1 cell line; pancreatic ductal carcinoma; phagocytosis; promoter region; tumor escape; tumor microenvironment; tumor xenograft; animal; chemistry; drug effect; drug therapy; genetics; immunology; metabolism; pancreas tumor; pancreatic ductal carcinoma; pathology; tumor cell line
Campos de Estudio
Cita
Parés M,Martínez J,Candela V,SORIANO PM,GARCÍA A,Pallaruelo V,AZNAR E,MARTÍNEZ R,Fillat C. Folate- and aCD47-functionalized lipid nanoparticles efficiently deliver mRNA and remodel pancreatic tumor microenvironment. Biomed. Pharmacother. 2026. 194. 118919. IF:7,500. (1).