Desmoplastic tumor priming using clinical-stage corticosteroid liposomes

Inflammation is a hallmark of cancer. It contributes to a heterogeneous, hyperpermeable, and poorly perfused tumor vasculature, as well as to a dense and disorganized extracellular matrix, which together negatively affect drug delivery. Reasoning that glucocorticoids have pleiotropic effects, we use clinical-stage dexamethasone liposomes (LipoDex) to prime the tumor microenvironment for improved drug delivery and enhanced treatment efficacy. We show that LipoDex priming improves tumor vascular function and reduces extracellular matrix deposition. Single-cell sequencing corroborates LipoDex-mediated inhibition of pro-inflammatory, pro-angiogenic, and pro-fibrogenic gene expression in mononuclear cells, tumor-associated macrophages, and cancer-associated fibroblasts. Multimodal optical imaging illustrates that LipoDex pre-treatment increases the tumor accumulation and intratumoral distribution of subsequently administered polymeric and liposomal drug delivery systems. Using Doxil as a prototypic nanodrug, we finally show that LipoDex priming promotes antitumor treatment efficacy. Altogether, our findings demonstrate that desmoplastic tumors can be primed for improved drug targeting and therapy using clinical-stage glucocorticoid liposomes.

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Publication Details

Journal
Cell Biomaterials
Published
2025-04-01
DOI
https://doi.org/10.1016/j.celbio.2025.100051
Citations
2
Primary Topic
Sarcoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
3.04
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article

Desmoplastic tumor priming using clinical-stage corticosteroid liposomes

Quim Peña, Maike Wagner, Lorena Consolino, Roman A. Barmin et al.
2 citations
Cell Biomaterials
Sarcoma Diagnosis and Treatment
3.04
article

Desmoplastic tumor priming using clinical-stage corticosteroid liposomes

Quim Peña, Maike Wagner, Lorena Consolino, Roman A. Barmin, Felix Gremse, Tarun Ojha, Gideon J L Schaefer, Vertika Pathak, Fabian M. Kiessling, Rafael Kramann, Steffen K. Meurer, Diana Moeckel, Josbert M. Metselaar, Asmaa Said Elshafei, Josef Ehling, Federica De Lorenzi, Ralf Weiskirchen, Sara Elsafy, Robert Pola, Marek Weiler, Benjamin Theek, Michal Pechar, Tomáš Etrych, Fabian Peisker, Tim Caspers, Twan Lammers, Elena Rama, Rahaf Mihyar, Gert Storm, Paolo Ceccarini
article en
2 citations

Abstract

Inflammation is a hallmark of cancer. It contributes to a heterogeneous, hyperpermeable, and poorly perfused tumor vasculature, as well as to a dense and disorganized extracellular matrix, which together negatively affect drug delivery. Reasoning that glucocorticoids have pleiotropic effects, we use clinical-stage dexamethasone liposomes (LipoDex) to prime the tumor microenvironment for improved drug delivery and enhanced treatment efficacy. We show that LipoDex priming improves tumor vascular function and reduces extracellular matrix deposition. Single-cell sequencing corroborates LipoDex-mediated inhibition of pro-inflammatory, pro-angiogenic, and pro-fibrogenic gene expression in mononuclear cells, tumor-associated macrophages, and cancer-associated fibroblasts. Multimodal optical imaging illustrates that LipoDex pre-treatment increases the tumor accumulation and intratumoral distribution of subsequently administered polymeric and liposomal drug delivery systems. Using Doxil as a prototypic nanodrug, we finally show that LipoDex priming promotes antitumor treatment efficacy. Altogether, our findings demonstrate that desmoplastic tumors can be primed for improved drug targeting and therapy using clinical-stage glucocorticoid liposomes.

Cell BiomaterialsVol. 1(3)
National University of Singapore (SG), Utrecht University (NL), Czech Academy of Sciences, Institute of Macromolecular Chemistry (CZ), RWTH Aachen University (DE), University of Twente (NL), FH Aachen (DE)
Good health and well-being
Openalex Percentile: Top 10%
Sarcoma Diagnosis and Treatment
3.04
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