Impact of molecular weight on the intrinsic immunogenic activity of poly(beta amino esters).
J Biomed Mater Res A
; 105(4): 1219-1229, 2017 04.
Article
in En
| MEDLINE
| ID: mdl-27977902
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 â¼1500-3000 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Polymers
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Dendritic Cells
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Drug Carriers
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Histocompatibility Antigens Class II
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Antigens, CD
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Gene Expression Regulation
Limits:
Animals
Language:
En
Journal:
J Biomed Mater Res A
Journal subject:
ENGENHARIA BIOMEDICA
Year:
2017
Type:
Article