Modulation of immunogenicity of poly(sarcosine) displayed on various nanoparticle surfaces due to different physical properties

Abstract

Poly(sarcosine) displayed on polymeric micelle is reported to trigger a T cell-independent type2 reaction with B1a cells in the mice to produce IgM and IgG3 antibodies. In addition to polymeric micelle, three kinds of vesicles displaying poly(sarcosine) on surface were prepared here to evaluate the amounts and avidities of IgM and IgG3, which were produced in mice, to correlate them with physical properties of the molecular assemblies. The largest amount of IgM was produced after twice administrations of a polymeric micelle of 35 nm diameter (G1). On the other hand, the production amount of IgG3 became the largest after twice administrations of G3 (vesicle of 229 nm diameter) or G4 (vesicle of 85 nm diameter). The augmented avidity of IgG3 after the twice administrations compared with that at the single administration was the highest with G3. These differences in immune responses are discussed in terms of surface density of poly(sarcosine) chains, nanoparticle size, hydrophobic component of poly(L-lactic acid) or (Leu- or Val-Aib) , and membrane elasticity of the nanoparticles. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Solution Properties of Polysarcosine: From Absolute and Relative Molar Mass Determinations to Complement Activation

“…Since all of the aforementioned methods showed comparable solution properties of PEG and pSar, we were interested in comparing biological properties of pSar to PEG. Our groups and others have investigated the cytotoxic properties of pSar homopolymers and various other pSar containing polymer architectures. ,− Kimura and co-workers demonstrated nicely that pSar-based micelles can have enhanced circulation times in mice, indicating the absence of acute immune responses to pSar. − In addition, Sela and co-workers demonstrated nicely that the immunogenicity of peptides is reduced upon conjugation of pSar . In terms of immune responses toward pSar the Kimura lab could not detect the formation of antibodies upon repeated injections .…”

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?

“…This metabolic clearance correlated with production of IgM and IgG3 which bound to PSar and persisted for 6 months after the first administration. Furthermore, the immunogenicity of PSar was found to vary with the type of particle (polymeric micelles or vesicular), the hydrodynamic diameter and the membrane elasticity (Kim et al, 2017).…”