Cargando…

Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages

Many cells possess the ability to engulf and incorporate particles by phagocytosis. This active process is characteristic of microorganisms as well as higher order species. In mammals, monocytes, macrophages, and microglia are among the so-called professional phagocytes. In addition, cells such as f...

Descripción completa

Detalles Bibliográficos
Autores principales: Wendler, Astrid, James, Nicholas, Jones, Michael H., Pernstich, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521757/
https://www.ncbi.nlm.nih.gov/pubmed/37849947
http://dx.doi.org/10.34133/2021/9816485
_version_ 1785110204371697664
author Wendler, Astrid
James, Nicholas
Jones, Michael H.
Pernstich, Christian
author_facet Wendler, Astrid
James, Nicholas
Jones, Michael H.
Pernstich, Christian
author_sort Wendler, Astrid
collection PubMed
description Many cells possess the ability to engulf and incorporate particles by phagocytosis. This active process is characteristic of microorganisms as well as higher order species. In mammals, monocytes, macrophages, and microglia are among the so-called professional phagocytes. In addition, cells such as fibroblast and chondrocytes are classified as nonprofessional phagocytes. Professional phagocytes play important roles in both the innate and adaptive immune responses, wound healing, and tissue homeostasis. Consequently, these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases. Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation. Consequently, efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis. However, this approach carries significant technical challenges, particularly for protein cargos. We have focused on the development of nanoscale cocrystalline protein depots, known as PODS®, that contain protein cargos, including cytokines. Here, we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes, such as highly sustained release of cargo, that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery. Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response. Moreover, the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic cells. The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases.
format Online
Article
Text
id pubmed-10521757
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher AAAS
record_format MEDLINE/PubMed
spelling pubmed-105217572023-10-17 Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages Wendler, Astrid James, Nicholas Jones, Michael H. Pernstich, Christian Biodes Res Research Article Many cells possess the ability to engulf and incorporate particles by phagocytosis. This active process is characteristic of microorganisms as well as higher order species. In mammals, monocytes, macrophages, and microglia are among the so-called professional phagocytes. In addition, cells such as fibroblast and chondrocytes are classified as nonprofessional phagocytes. Professional phagocytes play important roles in both the innate and adaptive immune responses, wound healing, and tissue homeostasis. Consequently, these cells are increasingly studied as targets and vectors of therapeutic intervention to treat a range of diseases. Professional phagocytes are notoriously difficult to transfect limiting their study and manipulation. Consequently, efforts have shifted towards the development of nanoparticles to deliver a cargo to phagocytic cells via phagocytosis. However, this approach carries significant technical challenges, particularly for protein cargos. We have focused on the development of nanoscale cocrystalline protein depots, known as PODS®, that contain protein cargos, including cytokines. Here, we show that PODS are readily phagocytosed by nonprofessional as well as professional phagocytic cells and have attributes, such as highly sustained release of cargo, that suggest potential utility for the study and exploitation of phagocytic cells for drug delivery. Monocytes and macrophages that ingest PODS retain normal characteristics including a robust chemotactic response. Moreover, the PODS-cytokine cargo is secreted by the loaded cell at a level sufficient to modulate the behavior of surrounding nonphagocytic cells. The results presented here demonstrate the potential of PODS nanoparticles as a novel molecular tool for the study and manipulation of phagocytic cells and for the development of Trojan horse immunotherapy strategies to treat cancer and other diseases. AAAS 2021-05-14 /pmc/articles/PMC10521757/ /pubmed/37849947 http://dx.doi.org/10.34133/2021/9816485 Text en Copyright © 2021 Astrid Wendler et al. https://creativecommons.org/licenses/by/4.0/Exclusive Licensee Nanjing Agricultural University. Distributed under a Creative Commons Attribution License (CC BY 4.0). (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Research Article
Wendler, Astrid
James, Nicholas
Jones, Michael H.
Pernstich, Christian
Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages
title Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages
title_full Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages
title_fullStr Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages
title_full_unstemmed Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages
title_short Phagocytosed Polyhedrin-Cytokine Cocrystal Nanoparticles Provide Sustained Secretion of Bioactive Cytokines from Macrophages
title_sort phagocytosed polyhedrin-cytokine cocrystal nanoparticles provide sustained secretion of bioactive cytokines from macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521757/
https://www.ncbi.nlm.nih.gov/pubmed/37849947
http://dx.doi.org/10.34133/2021/9816485
work_keys_str_mv AT wendlerastrid phagocytosedpolyhedrincytokinecocrystalnanoparticlesprovidesustainedsecretionofbioactivecytokinesfrommacrophages
AT jamesnicholas phagocytosedpolyhedrincytokinecocrystalnanoparticlesprovidesustainedsecretionofbioactivecytokinesfrommacrophages
AT jonesmichaelh phagocytosedpolyhedrincytokinecocrystalnanoparticlesprovidesustainedsecretionofbioactivecytokinesfrommacrophages
AT pernstichchristian phagocytosedpolyhedrincytokinecocrystalnanoparticlesprovidesustainedsecretionofbioactivecytokinesfrommacrophages