Polyglycidol-Stabilized Nanoparticles as a Promising Alternative to Nanoparticle PEGylation: Polymer Synthesis and Protein Fouling Considerations

Author(s)

Du, Haiqin ^[1] ; de Oliveira, Fernando A. ^[2] ; Albuquerque, Lindomar J. C. ^[2] ; Tresset, Guillaume ^[3] ; Pavlova, Ewa ^[4] ; Huin, Cecile ^{[1, 5]} ; Guegan, Philippe ^[1] ; Giacomelli, Fernando C. ^{[2, 1]}

Affiliation

^[1] Sorbonne Univ, Inst Parisien Chim Mol, Equipe Chim Polymeres, CNRS, UMR 8232, F-75252 Paris - France

^[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[3] Univ Paris Saclay, Univ Paris Sud, CNRS, Lab Phys Solides, F-91400 Orsay - France

^[4] Inst Macromol Chem, Prague 16206 - Czech Republic

^[5] Univ Paris Saclay, Univ Evry Val Essonne, F-91000 Evry - France

• Document type: Journal article
• Source: Langmuir; v. 36, n. 5, p. 1266-1278, FEB 11 2020.
• Web of Science Citations: 0

Abstract

We herein demonstrate the outstanding protein repelling characteristic of star-like micelles and polymersomes manufactured from amphiphilic block copolymers made by poly(butylene oxide) (PBO) hydrophobic segments and polyglycidol (PGL) hydrophilic outer shells. Although positively charged proteins (herein modeled by lysozyme) may adsorb onto the surface of micelles and polymersomes where the assemblies are stabilized by short PGL chains (degree of polymerization smaller than IS), the protein adsorption vanishes when the degree of polymerization of the hydrophilic segment (PGL) is higher than similar to 20, regardless the morphology. This has been probed by using three different model proteins which are remarkably different concerning molecular weight, size, and zeta potential (bovine serum albumin (BSA), lysozyme, and immunoglobulin G (IgG)). Indeed, the adsorption of the most abundant plasma protein (herein modeled as BSA) is circumvented even by using very short PGL shells due to the highly negative zeta potential of the produced assemblies which presumably promote protein-nanoparticle electrostatic repulsion. The negative zeta potential, on the other hand, enables lysozyme adsorption, and the phenomenon is governed by electrostatic forces as evidenced by isothermal titration calorimetry. Nevertheless, the protein coating can be circumvented by slightly increasing the degree of polymerization of the hydrophilic segment. Notably, the PGL length required to circumvent protein fouling is significantly smaller than the one required for PEO. This feature and the safety concerns regarding the synthetic procedures on the preparation of poly(ethylene oxide)-based amphiphilic copolymers might make polyglycidol a promising alternative toward the production of nonfouling spherical particles. (AU)

• FAPESP's process: 18/11038-2 - Polymer colloids in biological environments: from Polymer Synthesis to nanobiointerfaces
• Grantee: Fernando Carlos Giacomelli
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 17/00459-4 - Biophysicochemical interactions at the nanobiointerface: the effect of surface features and protein corona on the cellular uptake of polymeric assemblies
• Grantee: Fernando Carlos Giacomelli
• Support Opportunities: Regular Research Grants