期刊
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
卷 105, 期 4, 页码 1219-1229出版社
WILEY
DOI: 10.1002/jbm.a.35970
关键词
poly(beta amino ester); dendritic cell and lymphocyte; nanoparticle and microparticle; degradable biomaterial; immunology and vaccine
资金
- American Association of Pharmaceutical Scientists
- National Science Foundation CAREER Award [CAREER 1351688]
- Alliance for Cancer Gene Therapy [15051543]
- Damon Runyon Foundation [DRR3415]
- Melanoma Research Alliance [348963]
- Alex's Lemonade Stand Foundation for Childhood Cancer [27120]
- National Multiple Sclerosis Society [RG-1501-02968]
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 similar to 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. (C) 2017 Wiley Periodicals, Inc.
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