Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles

Optimizing the biological identity of nanoparticles (NPs) for efficient tumor uptake remains challenging. The controlled formation of a protein corona on NPs through protein absorption from biofluids could favor a biological identity that enables tumor accumulation. To increase the diversity of prot...

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Main Authors: Daniel Nierenberg, Orielyz Flores, David Fox, Yuen Yee Li Sip, Caroline M. Finn, Heba Ghozlan, Amanda Cox, Melanie Coathup, Karl Kai McKinstry, Lei Zhai, Annette R. Khaled
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Biomimetics
Subjects:
Online Access:https://www.mdpi.com/2313-7673/7/4/219
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author Daniel Nierenberg
Orielyz Flores
David Fox
Yuen Yee Li Sip
Caroline M. Finn
Heba Ghozlan
Amanda Cox
Melanie Coathup
Karl Kai McKinstry
Lei Zhai
Annette R. Khaled
author_facet Daniel Nierenberg
Orielyz Flores
David Fox
Yuen Yee Li Sip
Caroline M. Finn
Heba Ghozlan
Amanda Cox
Melanie Coathup
Karl Kai McKinstry
Lei Zhai
Annette R. Khaled
author_sort Daniel Nierenberg
collection DOAJ
description Optimizing the biological identity of nanoparticles (NPs) for efficient tumor uptake remains challenging. The controlled formation of a protein corona on NPs through protein absorption from biofluids could favor a biological identity that enables tumor accumulation. To increase the diversity of proteins absorbed by NPs, sera derived from Influenza A virus (IAV)-infected mice were used to pre-coat NPs formed using a hyperbranched polyester polymer (HBPE-NPs). HBPE-NPs, encapsulating a tracking dye or cancer drug, were treated with sera from days 3–6 of IAV infection (VS3-6), and uptake of HBPE-NPs by breast cancer cells was examined. Cancer cells demonstrated better uptake of HBPE-NPs pre-treated with VS3-6 over polyethylene glycol (PEG)-HBPE-NPs, a standard NP surface modification. The uptake of VS5 pre-treated HBPE-NPs by monocytic cells (THP-1) was decreased over PEG-HBPE-NPs. VS5-treated HBPE-NPs delivered a cancer drug more efficiently and displayed better <i>in vivo</i> distribution over controls, remaining stable even after interacting with endothelial cells. Using a proteomics approach, proteins absorbed from sera-treated HBPE-NPs were identified, such as thrombospondin-1 (TSP-1), that could bind multiple cancer cell receptors. Our findings indicate that serum collected during an immune response to infection is a rich source of macromolecules that are absorbed by NPs and modulate their biological identity, achieving rationally designed uptake by targeted cell types.
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spelling doaj.art-14948fc2c5f841329c43e0ba2b9cbce62023-11-24T13:31:40ZengMDPI AGBiomimetics2313-76732022-11-017421910.3390/biomimetics7040219Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric NanoparticlesDaniel Nierenberg0Orielyz Flores1David Fox2Yuen Yee Li Sip3Caroline M. Finn4Heba Ghozlan5Amanda Cox6Melanie Coathup7Karl Kai McKinstry8Lei Zhai9Annette R. Khaled10Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USANanoScience Technology Science Center, University of Central Florida, Orlando, FL 32826, USANanoScience Technology Science Center, University of Central Florida, Orlando, FL 32826, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USABiionix Cluster and Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL 32827, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USANanoScience Technology Science Center, University of Central Florida, Orlando, FL 32826, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USAOptimizing the biological identity of nanoparticles (NPs) for efficient tumor uptake remains challenging. The controlled formation of a protein corona on NPs through protein absorption from biofluids could favor a biological identity that enables tumor accumulation. To increase the diversity of proteins absorbed by NPs, sera derived from Influenza A virus (IAV)-infected mice were used to pre-coat NPs formed using a hyperbranched polyester polymer (HBPE-NPs). HBPE-NPs, encapsulating a tracking dye or cancer drug, were treated with sera from days 3–6 of IAV infection (VS3-6), and uptake of HBPE-NPs by breast cancer cells was examined. Cancer cells demonstrated better uptake of HBPE-NPs pre-treated with VS3-6 over polyethylene glycol (PEG)-HBPE-NPs, a standard NP surface modification. The uptake of VS5 pre-treated HBPE-NPs by monocytic cells (THP-1) was decreased over PEG-HBPE-NPs. VS5-treated HBPE-NPs delivered a cancer drug more efficiently and displayed better <i>in vivo</i> distribution over controls, remaining stable even after interacting with endothelial cells. Using a proteomics approach, proteins absorbed from sera-treated HBPE-NPs were identified, such as thrombospondin-1 (TSP-1), that could bind multiple cancer cell receptors. Our findings indicate that serum collected during an immune response to infection is a rich source of macromolecules that are absorbed by NPs and modulate their biological identity, achieving rationally designed uptake by targeted cell types.https://www.mdpi.com/2313-7673/7/4/219drug deliverytumorpaclitaxelprotein coronananomedicine
spellingShingle Daniel Nierenberg
Orielyz Flores
David Fox
Yuen Yee Li Sip
Caroline M. Finn
Heba Ghozlan
Amanda Cox
Melanie Coathup
Karl Kai McKinstry
Lei Zhai
Annette R. Khaled
Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles
Biomimetics
drug delivery
tumor
paclitaxel
protein corona
nanomedicine
title Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles
title_full Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles
title_fullStr Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles
title_full_unstemmed Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles
title_short Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles
title_sort macromolecules absorbed from influenza infection based sera modulate the cellular uptake of polymeric nanoparticles
topic drug delivery
tumor
paclitaxel
protein corona
nanomedicine
url https://www.mdpi.com/2313-7673/7/4/219
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