ArticleDrug delivery and translational research2026
Glucocorticoid receptor-targeted liposomal delivery of wnt/β-catenin pathway inhibitor selectively induces efficient colorectal tumor regression.
Article in Drug delivery and translational research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Evolution of Gastrointestinal Inflammatory Diseases and Neoplasm Burden in Super-Elderly Populations: Integrated GBD 2023, CHARLS, and CLHLS Analyses of China and G20 Countries.Molecular medicine (Cambridge, Mass.) · 2026Article
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Authors and funding
6 authors.
Funding
Abstract
Wnt/β-catenin signaling pathway is a highly conserved developmental pathway. This pathway is also involved in colorectal cancer and thus its selective targeting to cancer cells, albeit the risk involved, can serve as a promising therapeutic approach. Glucocorticoid receptor (GR) is a nuclear hormone receptor present in both cancer and non-cancer cells. Previously, we showed that cancer cell-associated GR, without eliciting any effect in normal cells, could be targeted for selective drug-sensitization in cancer cells. Based on this unique feature, we intended to sensitize the wnt/β-catenin pathway by co-formulating a GR-targeted cationic liposomal formulation carrying dexamethasone, a synthetic GR-ligand, and a wnt/β-catenin pathway inhibitor, FH535, to form D1XFH formulation. The nanometric and positively charged D1XFH formulation selectively kills colorectal cancer cells at much lower FH535 concentration than free drug or drug-associated GR-non-targeted liposome, while exhibiting unique nuclear uptake, increased ROS generation, apoptosis and G2-M phase cell cycle arrest in cancer cells. Further, in vivo data shows enhanced tumor-specific localization of this formulation, significant tumor growth inhibition and increased mice survivability, signifying its efficacy and biocompatibility in mouse colon subcutaneous and orthotopic tumor models. Protein expression analysis reveals enhanced reversal of epithelial-to-mesenchymal transition (EMT) and inhibition of various downstream proteins of wnt/β-catenin pathway. Additionally, analysis of tumor lysate from D1XFH-treated group shows an increased Th1/Th2 ratio, indicating favorable, anti-tumor immune response. The formulation exhibits no sub-chronic toxicity against healthy mice. In overall, our data strongly suggest that the GR-targeted FH535 liposomal delivery can safely target the highly sensitive wnt/β-catenin pathway for effective treatment of colorectal tumor.
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