Surface decoration of red blood cells with maleimidophenyl‐polyethylene glycol facilitated by thiolation with iminothiolane: an approach to mask A, B, and D antigens to generate universal red blood cells

Abstract

Thiolation-mediated PEGylation of RBCs with Mal-Phe-PEG-5000 and Mal-Phe-PEG-20000 converts Group A Rh(D)+ and B Rh(D)+ RBCs into RBCs with serologic behavior comparable to Group O Rh(D)- RBCs that are considered as universal RBCs for transfusion.

Drug delivery by red blood cells: vascular carriers designed by mother nature

“…Masking against immune reaction to mismatched ABO antigens is the most challenging goal; in this setting, PEG-coating offered no protection and rather aggravated hemolysis in the initial studies191. Additional studies using alternative PEG-coupling techniques and combinations of PEG with different chain length produced encouraging results in masking ABO and Rh(D) blood group antigens192–194. More recently, even masking of xeno-antigens on RBC has been attempted, yet the outcome was not too encouraging195.…”

“…PEG coupling using sulfo-group chemistry192,194, insertion of lipid derivatives of PEG197 and other methods have also been developed186,198,199. Extent of “stealth” feature or masking increases proportionally to PEG length in the range 5–35 kD, branching and surface density200.…”

Pancreatic islet PEGylation as an immunological polymeric restraint

“…Based on the findings and hypotheses with PEGylation, Lee et al evaluated the clinical potential of a new combinatorial therapy based on PEGylation and immunosuppressant administration in an effort to minimize the dosages required [40,41,65,66]. The concept is that PEGylation can inhibit cell-mediated immune reactions, and immunosuppressant can attenuate the indirectly activated immune reactions, thereby showing the synergism of them and reducing the regimen of immunosuppressants [42] (Fig.…”

“…PEGylation, is that the conjugated PEG molecules protect islets from immune cell's attack because of its low interfacial free energy with water, its unique properties in aqueous solutions, its high surface mobility, and its substantial steric stabilization effects [34,35]. This immunologically protective strategy to the cell was originally applied to the surface modification of red blood cells (RBC) using PEG to chemically camouflage the antigenic determinants of RBC, thereby masking major and minor blood group antigens from host antibodies [36][37][38][39][40]. Based on such promising findings, PEGylation approach can be applied to islets without compromising viability and functionality [28,30,[41][42][43].…”

Molecular Engineering of Cell and Tissue Surfaces with Polymer Thin Films

“…Accordingly, covalent conjugation of PEG provides an excellent case study for illustrating some of the key challenges and design parameters associated with fabrication of covalently grafted polymer monolayers. Increased reaction efficiency has also been described using 2-iminothiolane (Traut's reagent) to convert surface amines to thiol groups to which maleimide-functionalized polymers can subsequently be attached [22]. Consequently, a large stoichiometric excess of reactive PEG is commonly used to increase the surface density of polymer chains immobilized to the cell surface [17].…”