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Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles
In drug delivery, the development of nanovesicles that combine both synthetic and cellular components provides added biocompatibility and targeting specificity in comparison to conventional synthetic carriers such as liposomes. Produced through the fusion of U937 monocytes’ membranes and synthetic l...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413569/ https://www.ncbi.nlm.nih.gov/pubmed/36015364 http://dx.doi.org/10.3390/pharmaceutics14081738 |
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author | Ou, Yi-Hsuan Liang, Jeremy Chng, Wei Heng Muthuramalingam, Ram Pravin Kumar Ng, Zi Xiu Lee, Choon Keong Neupane, Yub Raj Yau, Jia Ning Nicolette Zhang, Sitong Lou, Charles Kang Liang Huang, Chenyuan Wang, Jiong-Wei Pastorin, Giorgia |
author_facet | Ou, Yi-Hsuan Liang, Jeremy Chng, Wei Heng Muthuramalingam, Ram Pravin Kumar Ng, Zi Xiu Lee, Choon Keong Neupane, Yub Raj Yau, Jia Ning Nicolette Zhang, Sitong Lou, Charles Kang Liang Huang, Chenyuan Wang, Jiong-Wei Pastorin, Giorgia |
author_sort | Ou, Yi-Hsuan |
collection | PubMed |
description | In drug delivery, the development of nanovesicles that combine both synthetic and cellular components provides added biocompatibility and targeting specificity in comparison to conventional synthetic carriers such as liposomes. Produced through the fusion of U937 monocytes’ membranes and synthetic lipids, our nano-cell vesicle technology systems (nCVTs) showed promising results as targeted cancer treatment. However, no investigation has been conducted yet on the immunogenic profile and the uptake mechanisms of nCVTs. Hence, this study was aimed at exploring the potential cytotoxicity and immune cells’ activation by nCVTs, as well as the routes through which cells internalize these biohybrid systems. The endocytic pathways were selectively inhibited to establish if the presence of cellular components in nCVTs affected the internalization route in comparison to both liposomes (made up of synthetic lipids only) and nano-cellular membranes (made up of biological material only). As a result, nCVTs showed an 8-to-40-fold higher cellular internalization than liposomes within the first hour, mainly through receptor-mediated processes (i.e., clathrin- and caveolae-mediated endocytosis), and low immunostimulatory potential (as indicated by the level of IL-1α, IL-6, and TNF-α cytokines) both in vitro and in vivo. These data confirmed that nCVTs preserved surface cues from their parent U937 cells and can be rationally engineered to incorporate ligands that enhance the selective uptake and delivery toward target cells and tissues. |
format | Online Article Text |
id | pubmed-9413569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94135692022-08-27 Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles Ou, Yi-Hsuan Liang, Jeremy Chng, Wei Heng Muthuramalingam, Ram Pravin Kumar Ng, Zi Xiu Lee, Choon Keong Neupane, Yub Raj Yau, Jia Ning Nicolette Zhang, Sitong Lou, Charles Kang Liang Huang, Chenyuan Wang, Jiong-Wei Pastorin, Giorgia Pharmaceutics Article In drug delivery, the development of nanovesicles that combine both synthetic and cellular components provides added biocompatibility and targeting specificity in comparison to conventional synthetic carriers such as liposomes. Produced through the fusion of U937 monocytes’ membranes and synthetic lipids, our nano-cell vesicle technology systems (nCVTs) showed promising results as targeted cancer treatment. However, no investigation has been conducted yet on the immunogenic profile and the uptake mechanisms of nCVTs. Hence, this study was aimed at exploring the potential cytotoxicity and immune cells’ activation by nCVTs, as well as the routes through which cells internalize these biohybrid systems. The endocytic pathways were selectively inhibited to establish if the presence of cellular components in nCVTs affected the internalization route in comparison to both liposomes (made up of synthetic lipids only) and nano-cellular membranes (made up of biological material only). As a result, nCVTs showed an 8-to-40-fold higher cellular internalization than liposomes within the first hour, mainly through receptor-mediated processes (i.e., clathrin- and caveolae-mediated endocytosis), and low immunostimulatory potential (as indicated by the level of IL-1α, IL-6, and TNF-α cytokines) both in vitro and in vivo. These data confirmed that nCVTs preserved surface cues from their parent U937 cells and can be rationally engineered to incorporate ligands that enhance the selective uptake and delivery toward target cells and tissues. MDPI 2022-08-20 /pmc/articles/PMC9413569/ /pubmed/36015364 http://dx.doi.org/10.3390/pharmaceutics14081738 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ou, Yi-Hsuan Liang, Jeremy Chng, Wei Heng Muthuramalingam, Ram Pravin Kumar Ng, Zi Xiu Lee, Choon Keong Neupane, Yub Raj Yau, Jia Ning Nicolette Zhang, Sitong Lou, Charles Kang Liang Huang, Chenyuan Wang, Jiong-Wei Pastorin, Giorgia Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles |
title | Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles |
title_full | Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles |
title_fullStr | Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles |
title_full_unstemmed | Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles |
title_short | Investigations on Cellular Uptake Mechanisms and Immunogenicity Profile of Novel Bio-Hybrid Nanovesicles |
title_sort | investigations on cellular uptake mechanisms and immunogenicity profile of novel bio-hybrid nanovesicles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413569/ https://www.ncbi.nlm.nih.gov/pubmed/36015364 http://dx.doi.org/10.3390/pharmaceutics14081738 |
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