The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents
Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/9/12/766 |
| _version_ | 1797461427152224256 |
|---|---|
| author | Nagwa El-Baz Betty M. Nunn Paula J. Bates Martin G. O’Toole |
| author_facet | Nagwa El-Baz Betty M. Nunn Paula J. Bates Martin G. O’Toole |
| author_sort | Nagwa El-Baz |
| collection | DOAJ |
| description | Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs. |
| first_indexed | 2024-03-09T17:19:16Z |
| format | Article |
| id | doaj.art-83db1c67bb9046aa95ba65807b083d3c |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-09T17:19:16Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-83db1c67bb9046aa95ba65807b083d3c2023-11-24T13:20:39ZengMDPI AGBioengineering2306-53542022-12-0191276610.3390/bioengineering9120766The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast AgentsNagwa El-Baz0Betty M. Nunn1Paula J. Bates2Martin G. O’Toole3Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USADepartment of Bioengineering, University of Louisville, Louisville, KY 40292, USADepartment of Medicine, University of Louisville, Louisville, KY 40202, USADepartment of Bioengineering, University of Louisville, Louisville, KY 40292, USAGold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs.https://www.mdpi.com/2306-5354/9/12/766gold nanoparticleAS1411gadolinium chelatepolyethylene glycolcancer-targetedopsonization |
| spellingShingle | Nagwa El-Baz Betty M. Nunn Paula J. Bates Martin G. O’Toole The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents Bioengineering gold nanoparticle AS1411 gadolinium chelate polyethylene glycol cancer-targeted opsonization |
| title | The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents |
| title_full | The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents |
| title_fullStr | The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents |
| title_full_unstemmed | The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents |
| title_short | The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents |
| title_sort | impact of pegylation on cellular uptake and in vivo biodistribution of gold nanoparticle mri contrast agents |
| topic | gold nanoparticle AS1411 gadolinium chelate polyethylene glycol cancer-targeted opsonization |
| url | https://www.mdpi.com/2306-5354/9/12/766 |
| work_keys_str_mv | AT nagwaelbaz theimpactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT bettymnunn theimpactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT paulajbates theimpactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT martingotoole theimpactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT nagwaelbaz impactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT bettymnunn impactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT paulajbates impactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents AT martingotoole impactofpegylationoncellularuptakeandinvivobiodistributionofgoldnanoparticlemricontrastagents |