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10.1208/s12248-014-9697-1 http://scihub22266oqcxt.onion/10.1208/s12248-014-9697-1 C4365097!4365097!25501498     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       AAPS+J 2015 ; 17 (2): 358-69 Nephropedia Template TP {{tp|p=25501498|t=2015. Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive, Endosomolytic Polymer Nanoparticles |pdf=|usr=}}{{25501498}} gab.com Text Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive, Endosomolytic Polymer Nanoparticles JO: AAPS J http://www.kidney.de/pget.php?&tw=1&pmid=25501498 #FOAvip Protein-based vaccines offer a number of important advantages over organism-based vaccines but generally elicit poor CD8+ T cell responses. We have previously demonstrated that pH-responsive, endosomolytic polymers can enhance protein antigen delivery to major histocompatibility complex class I (MHC-I) antigen presentation pathways thereby augmenting CD8+ T cell responses following immunization. Here, we describe a new family of nanocarriers for protein antigen delivery assembled using architecturally distinct pH-responsive polymers. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize linear, hyperbranched, and core-crosslinked copolymers of 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) that were subsequently chain extended with a hydrophilic N,N-dimethylacrylamide (DMA) segment copolymerized with thiol-reactive pyridyl disulfide (PDS) groups. In aqueous solution, polymer chains assembled into 25 nm micellar nanoparticles and enabled efficient and reducible conjugation of a thiolated protein antigen, ovalbumin. Polymers demonstrated pH-dependent membrane-destabilizing activity in an erythrocyte lysis assay, with the hyperbranched and cross-linked polymer architectures exhibiting significantly higher hemolysis at pH???7.0 than the linear diblock. Antigen delivery with the hyperbranched and cross-linked polymer architecture enhanced in vitro MHC-I antigen presentation relative to free antigen, whereas the linear construct did not have a discernible effect. The hyperbranched system elicited a four- to fivefold increase in MHC-I presentation relative to the cross-linked architecture, demonstrating the superior capacity of the hyperbranched architecture in enhancing MHC-I presentation. This work demonstrates that the architecture of pH-responsive, endosomolytic polymers can have dramatic effects on intracellular antigen delivery, and offers a promising strategy for enhancing CD8+ T cell responses to protein-based vaccines.Electronic supplementary material: The online version of this article (doi:10.1208/s12248-014-9697-1) contains supplementary material, which is available to authorized users. Twit Text FOAVip Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive, Endosomolytic Polymer Nanoparticles ????AAPS J http://www.kidney.de/pget.php?&tw=1&pmid=25501498 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25501498 #FOAvip English Wikipedia <ref>{{Cite pmid|25501498}}</ref> Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive, Endosomolytic Polymer Nanoparticles #MMPMID25501498 Wilson JT; Postma A; Keller S; Convertine AJ; Moad G; Rizzardo E; Meagher L; Chiefari J; Stayton PS AAPS J 2015[Mar]; 17 (2): 358-69 PMID25501498show ga Protein-based vaccines offer a number of important advantages over organism-based vaccines but generally elicit poor CD8+ T cell responses. We have previously demonstrated that pH-responsive, endosomolytic polymers can enhance protein antigen delivery to major histocompatibility complex class I (MHC-I) antigen presentation pathways thereby augmenting CD8+ T cell responses following immunization. Here, we describe a new family of nanocarriers for protein antigen delivery assembled using architecturally distinct pH-responsive polymers. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize linear, hyperbranched, and core-crosslinked copolymers of 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) that were subsequently chain extended with a hydrophilic N,N-dimethylacrylamide (DMA) segment copolymerized with thiol-reactive pyridyl disulfide (PDS) groups. In aqueous solution, polymer chains assembled into 25 nm micellar nanoparticles and enabled efficient and reducible conjugation of a thiolated protein antigen, ovalbumin. Polymers demonstrated pH-dependent membrane-destabilizing activity in an erythrocyte lysis assay, with the hyperbranched and cross-linked polymer architectures exhibiting significantly higher hemolysis at pH???7.0 than the linear diblock. Antigen delivery with the hyperbranched and cross-linked polymer architecture enhanced in vitro MHC-I antigen presentation relative to free antigen, whereas the linear construct did not have a discernible effect. The hyperbranched system elicited a four- to fivefold increase in MHC-I presentation relative to the cross-linked architecture, demonstrating the superior capacity of the hyperbranched architecture in enhancing MHC-I presentation. This work demonstrates that the architecture of pH-responsive, endosomolytic polymers can have dramatic effects on intracellular antigen delivery, and offers a promising strategy for enhancing CD8+ T cell responses to protein-based vaccines.Electronic supplementary material: The online version of this article (doi:10.1208/s12248-014-9697-1) contains supplementary material, which is available to authorized users. äEnhancement of MHC-I Antigen Presentation via Architectural Control of(epmc).pdf DeepDyve Pubget Overpricing