Nanoparticle Surface Engineering with Heparosan Polysaccharide Reduces Serum Protein Adsorption and Enhances Cellular Uptake

Overview

Journal Nano Lett

Publisher American Chemical Society

Specialty Biotechnology

Date 2022 Feb 15

PMID 35166110

Authors

Wen Yang

Lin Wang

Mulin Fang

Vinit Sheth

Yushan Zhang

Alyssa M Holden

Nathan D Donahue

Dixy E Green

Alex N Frickenstein

Evan M Mettenbrink

Tyler A Schwemley

Emmy R Francek

Majood Haddad

Md Nazir Hossen

Shirsha Mukherjee

Si Wu

Paul L DeAngelis

Stefan Wilhelm

Affiliations

Soon will be listed here.

Abstract

Nanoparticle modification with poly(ethylene glycol) (PEG) is a widely used surface engineering strategy in nanomedicine. However, since the artificial PEG polymer may adversely impact nanomedicine safety and efficacy, alternative surface modifications are needed. Here, we explored the "self" polysaccharide heparosan (HEP) to prepare colloidally stable HEP-coated nanoparticles, including gold and silver nanoparticles and liposomes. We found that the HEP-coating reduced the nanoparticle protein corona formation as efficiently as PEG coatings upon serum incubation. Liquid chromatography-mass spectrometry revealed the protein corona profiles. Heparosan-coated nanoparticles exhibited up to 230-fold higher uptake in certain innate immune cells, but not in other tested cell types, than PEGylated nanoparticles. No noticeable cytotoxicity was observed. Serum proteins did not mediate the high cell uptake of HEP-coated nanoparticles. Our work suggests that HEP polymers may be an effective surface modification technology for nanomedicines to safely and efficiently target certain innate immune cells.

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References

Zhang P, Sun F, Liu S, Jiang S . Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation. J Control Release. 2016; 244(Pt B):184-193. PMC: 5747248. DOI: 10.1016/j.jconrel.2016.06.040. View

Chen L, Hong W, Ren W, Xu T, Qian Z, He Z . Recent progress in targeted delivery vectors based on biomimetic nanoparticles. Signal Transduct Target Ther. 2021; 6(1):225. PMC: 8182741. DOI: 10.1038/s41392-021-00631-2. View

Sheth V, Wang L, Bhattacharya R, Mukherjee P, Wilhelm S . Strategies for Delivering Nanoparticles across Tumor Blood Vessels. Adv Funct Mater. 2023; 31(8). PMC: 10187772. DOI: 10.1002/adfm.202007363. View

Xu Q, Ensign L, Boylan N, Schon A, Gong X, Yang J . Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex Vivo and Distribution in Vivo. ACS Nano. 2015; 9(9):9217-27. PMC: 4890729. DOI: 10.1021/acsnano.5b03876. View

Fang R, Kroll A, Gao W, Zhang L . Cell Membrane Coating Nanotechnology. Adv Mater. 2018; 30(23):e1706759. PMC: 5984176. DOI: 10.1002/adma.201706759. View

Yang W, Wang L, Mettenbrink E, DeAngelis P, Wilhelm S . Nanoparticle Toxicology. Annu Rev Pharmacol Toxicol. 2020; 61:269-289. DOI: 10.1146/annurev-pharmtox-032320-110338. View

Veronese F, Pasut G . PEGylation, successful approach to drug delivery. Drug Discov Today. 2005; 10(21):1451-8. DOI: 10.1016/S1359-6446(05)03575-0. View

Larson T, Joshi P, Sokolov K . Preventing protein adsorption and macrophage uptake of gold nanoparticles via a hydrophobic shield. ACS Nano. 2012; 6(10):9182-90. PMC: 3517292. DOI: 10.1021/nn3035155. View

Kozma G, Meszaros T, Vashegyi I, Fulop T, orfi E, Dezsi L . Pseudo-anaphylaxis to Polyethylene Glycol (PEG)-Coated Liposomes: Roles of Anti-PEG IgM and Complement Activation in a Porcine Model of Human Infusion Reactions. ACS Nano. 2019; 13(8):9315-9324. DOI: 10.1021/acsnano.9b03942. View

10.

Walkey C, Olsen J, Guo H, Emili A, Chan W . Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J Am Chem Soc. 2011; 134(4):2139-47. DOI: 10.1021/ja2084338. View

11.

Wilhelm S, Hirsch T, Patterson W, Scheucher E, Mayr T, Wolfbeis O . Multicolor upconversion nanoparticles for protein conjugation. Theranostics. 2013; 3(4):239-48. PMC: 3630524. DOI: 10.7150/thno.5113. View

12.

Sindhwani S, Syed A, Ngai J, Kingston B, Maiorino L, Rothschild J . The entry of nanoparticles into solid tumours. Nat Mater. 2020; 19(5):566-575. DOI: 10.1038/s41563-019-0566-2. View

13.

Shimabukuro T, Cole M, Su J . Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US-December 14, 2020-January 18, 2021. JAMA. 2021; 325(11):1101-1102. PMC: 8890485. DOI: 10.1001/jama.2021.1967. View

14.

Wang Z, Dordick J, Linhardt R . Escherichia coli K5 heparosan fermentation and improvement by genetic engineering. Bioeng Bugs. 2011; 2(1):63-7. PMC: 3127022. DOI: 10.4161/bbug.2.1.14201. View

15.

Sang W, Zhang Z, Dai Y, Chen X . Recent advances in nanomaterial-based synergistic combination cancer immunotherapy. Chem Soc Rev. 2019; 48(14):3771-3810. DOI: 10.1039/c8cs00896e. View

16.

Zhang Y, Wu J, Lazarovits J, Chan W . An Analysis of the Binding Function and Structural Organization of the Protein Corona. J Am Chem Soc. 2020; 142(19):8827-8836. DOI: 10.1021/jacs.0c01853. View

17.

Qiu L, Shan X, Long M, Ahmed K, Zhao L, Mao J . Elucidation of cellular uptake and intracellular trafficking of heparosan polysaccharide-based micelles in various cancer cells. Int J Biol Macromol. 2019; 130:755-764. DOI: 10.1016/j.ijbiomac.2019.02.133. View

18.

Syed A, MacMillan P, Ngai J, Wilhelm S, Sindhwani S, Kingston B . Liposome Imaging in Optically Cleared Tissues. Nano Lett. 2020; 20(2):1362-1369. DOI: 10.1021/acs.nanolett.9b04853. View

19.

Schottler S, Becker G, Winzen S, Steinbach T, Mohr K, Landfester K . Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers. Nat Nanotechnol. 2016; 11(4):372-7. DOI: 10.1038/nnano.2015.330. View

20.

Dai Q, Wilhelm S, Ding D, Syed A, Sindhwani S, Zhang Y . Quantifying the Ligand-Coated Nanoparticle Delivery to Cancer Cells in Solid Tumors. ACS Nano. 2018; 12(8):8423-8435. DOI: 10.1021/acsnano.8b03900. View