Journal article
Organelle Specific Macrophage Engineered Vesicles Differentially Reprogram Macrophage Polarization
Advanced healthcare materials, Vol.13(30), 2401906
12/2024
DOI: 10.1002/adhm.202401906
PMCID: PMC12988851
PMID: 39240019
Abstract
Abstract Tumor‐associated macrophages (TAMs) represent the majority of the immune cells present in the tumor microenvironment. These macrophages exhibit an anti‐inflammatory (M2)‐like physiological state and execute immune‐suppressive and tumor‐supporting properties. With TAMs being plastic, there is a growing interest in reprogramming them toward a pro‐inflammatory (M1)‐like phenotype that exhibits anti‐tumoral properties. Recent studies have demonstrated that both engineered vesicles derived from macrophages and endogenous extracellular vesicles produced by macrophages can be programmed to alter macrophage phenotype. Here it is demonstrated that pro‐inflammatory macrophage‐engineered subcellular vesicles (MEVs) have differential properties based on their organelle of origin. Endoplasmic reticulum specific MEVs (erMEVs) treated M2 macrophages exhibit enhanced pro‐inflammatory cytokine production compared to plasma membrane specific MEVs (pmMEVs) treated M2 macrophages. In addition, under in vitro co‐culture conditions, erMEVs elicit superior efficacy in suppressing the viability of cancer cells compared to the same concentration of pmMEVs. Furthermore, erMEVs and pmMEVs maintain differences in their membrane proteins, that regulate the repolarization efficacy of M2 macrophages toward an M1‐like phenotype. In addition, The M2 to M1 repolarizing efficacy of MEVs can be altered by changing the activity of the membrane proteins present on erMEVs or pmMEVs.
Details
- Title: Subtitle
- Organelle Specific Macrophage Engineered Vesicles Differentially Reprogram Macrophage Polarization
- Creators
- Khaga R. Neupane - University of KentuckySurya P. Aryal - University of KentuckyBrock T. Harvey - University of KentuckyGeraldine San Ramon - Loyola University ChicagoByeong Chun - Loyola University ChicagoJ. Robert McCorkle - University of KentuckyJill M. Kolesar - University of KentuckyPeter M. Kekenes-Huskey - Loyola University ChicagoChristopher I. Richards - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Advanced healthcare materials, Vol.13(30), 2401906
- DOI
- 10.1002/adhm.202401906
- PMID
- 39240019
- PMCID
- PMC12988851
- NLM abbreviation
- Adv Healthc Mater
- ISSN
- 2192-2640
- eISSN
- 2192-2659
- Publisher
- WILEY
- Grant note
- National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH): R35GM124977 (PK-H)
C.I.R. and J.M.L. acknowledge support from the Kentucky Network for Innovation & Commercialization (KYNETIC) and the Kentucky Pediatric Cancer Research Trust Fund (KYPCRTF). The authors thank the Light Microscopy Core at the University of Kentucky for assistance with confocal microscopy experiments. C.I.R. acknowledges support from the NIH (GM138837 and GM138882). The authors also thank Dr. Jennifer S. Moylan, Director of the Biomarker Analysis Lab at the University of Kentucky for providing access to the Meso Sector for MSD analysis. Research reported in this publication was supported by the Maximizing Investigators' Research Award (MIRA) (R35) from the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under grant number R35GM124977 (PK-H).
- Language
- English
- Electronic publication date
- 09/06/2024
- Date published
- 12/2024
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984701821002771
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