title: Impact of molecular weight on the intrinsic immunogenic activity of poly(beta amino esters).
abstract: Polymeric carriers are ubiquitously studied in vaccine and drug delivery to control the encapsulation, kinetics, and targeting of cargo. Recent research reveals many polymers can cause immunostimulatory and inflammatory responses, even in the absence of other immune signals. However, the extent to which this intrinsic immunogenicity evolves during degradation is understudied. Here we synthesized a small library of poly(beta amino esters) (PBAEs) that exhibit different starting molecular weights (MWs), but with similar and rapid degradation rates. Primary dendritic cells (DCs) treated with free PBAEs, either intact or degraded to form low MW fragments, were not activated. In contrast particles formed from PBAEs at different extents of degradation caused differential expression of classical DC activation markers (for example, CD40, CD80, CD86, MHCII), as well as antigen presentation. During degradation, activation levels changed with changing physicochemical properties (for example, MW, concentration, size, charge). Of note, irrespective of starting MW, immunogenicity peaked when the MW of degrading PBAEs decreased to a range of ∼1500-3000 Da. These findings could help inform design of future carriers that exploit the dynamic interactions with the immune system as materials degrade, leading to carriers that deliver cargo but also help direct the immune responses to vaccine or immunotherapy cargo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1219-1229, 2017.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.
authors.forename: James I
authors.initials: JI
authors.lastname: Andorko
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Pineault
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.|Department of Microbiology and Immunology, University of Maryland Medical School, Baltimore, Maryland.|Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland.|Biomedical Laboratory Research and Development, United States Department of Veterans Affairs, Baltimore, Maryland.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jewell
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D004337:Drug Carriers; D000949:Histocompatibility Antigens Class II; D011108:Polymers; C507253:poly(beta-amino ester)
keywords: degradable biomaterial; dendritic cell and lymphocyte; immunology and vaccine; nanoparticle and microparticle; poly(beta amino ester)