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Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes

Paper ID Volume ID Publish Year Pages File Format Full-Text
6721 513 2012 9 PDF Available
Title
Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes
Abstract

While current subunit vaccines successfully induce humoral immune responses, a need exists for vaccine strategies to elicit strong cell-mediated immunity to address diseases such as cancer and chronic viral infection. Polymersomes are stable vesicles composed of self-assembling block copolymers with tunable degradation properties allowing delivery of both hydrophilic (within vesicle interior) or hydrophobic (within vesicle membrane) payload molecules. Here we apply oxidation-sensitive nanoscale polymersomes for both antigen and adjuvant delivery to dendritic cell (DC) endosomes. Calcein-loaded polymersomes were observed to release their payload initially in multiple DC endosomal compartments and subsequently within the cytosol. With either the Toll-like receptor agonists gardiquimod or R848 as payloads within the polymersomes, release resulted in DC activation, as indicated by induction of inflammatory cytokine expression and upregulation of DC maturation surface markers: for example, the ability of gardiquimod to induce IL-6 and IL-12 cytokine expression by DCs was enhanced 10-fold when loaded within polymersomes. With the model antigen ovalbumin as a payload, release resulted in CD8+ T cell cross-priming by promoting protein antigen cross-presentation through MHC I, as indicated by activation of OT-I CD8+ T cells. Our results demonstrate that oxidation-sensitive polymersomes can function as a vaccine delivery platform for inducing cell-mediated antigen-specific immune responses.

Keywords
Immunomodulation; Copolymer; Self-assembly; Drug delivery
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Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 26, September 2012, Pages 6211–6219
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us