東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Local Administration of Biomaterials...

Li, Yuan-Ping Peter.

FindBook

Google Book

Amazon

博客來

Local Administration of Biomaterials for Inducing Antigen-Specific Immune Tolerance.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Local Administration of Biomaterials for Inducing Antigen-Specific Immune Tolerance./
作者:	Li, Yuan-Ping Peter.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	130 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-12, Section: B.
Contained By:	Dissertations Abstracts International82-12B.
標題:	Immunology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28497369
ISBN:	9798515271459

Local Administration of Biomaterials for Inducing Antigen-Specific Immune Tolerance.
Li, Yuan-Ping Peter.

Local Administration of Biomaterials for Inducing Antigen-Specific Immune Tolerance. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 130 p.

Source: Dissertations Abstracts International, Volume: 82-12, Section: B.

Thesis (Ph.D.)--Drexel University, 2021.

This item must not be sold to any third party vendors.

Current treatment options for autoimmune conditions most commonly employ the use of nonspecific immunosuppressive agents that have significant adverse side effects. Ideally, the goal of autoimmune therapies is to achieve lasting autoantigen-specific tolerance. Nanoparticle (NP)-based therapies have recently shown promise in several animal models, but unfortunately, none have yet been validated in humans, and a deeper understanding of how different nanomaterials affect tolerogenic pathways is still needed. In this thesis, immune system interactions with local subcutaneous administrations of different materials are studied in the context of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, with the ultimate goal of creating and optimizing treatments for autoimmunity.First, a simple subcutaneous injection of a nanoparticle fabricated from PLGA-PEG block copolymer containing only antigen was found to be sufficient to dramatically ameliorate EAE symptoms. The tolerogenic capability of this particle was surprising due to the lack of any tolerogenic drug and because previous studies using PLGA alone did not significantly ameliorate disease. Thus, it was hypothesized that intrinsic properties of PLGA-PEG facilitated tolerogenic responses in ways that other polymers do not. This provided the opportunity to directly compare the effects of PLGA-PEG, PLGA, and partial PLGA/PLGA-PEG nanoparticles on treating EAE and their in vitro and in vivo responses. PLGA-PEG-NPs ameliorated EAE in both an antigen- and material-specific manner. The particles also demonstrated decreased complement activation, increased spleen and lymph node localization, and decreased activation of co-stimulatory molecules in dendritic cells in vivo. Mice successfully treated with the PLGA-PEG-NPs exhibited decreased IL-17 inflammatory cytokine production in response to antigen restimulation ex vivo.In an effort to develop a platform to study local cell recruitment and to further improve tolerogenic responses, a macroporous alginate-based polymeric scaffold system was created. When incorporated with the cytokine GM-CSF, this system demonstrated the ability to recruit significant populations of dendritic cells in vivo, which are the most important cells in immunomodulation. The addition of antigen-loaded PLGA-PEG-NPs allowed the system to also reverse symptoms of EAE after the onset of disease. However, the scaffold system failed to demonstrate an improvement over PLGA-PEG-NPs alone. Overall, these studies will hopefully pave the way for future iterations of scaffold-based autoimmune treatments, a greater understanding of PLGA-based materials for inducing tolerance, and a promising and simple PLGA-PEG nanoparticle for treating autoimmunity.

ISBN: 9798515271459Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

Local administration

Local Administration of Biomaterials for Inducing Antigen-Specific Immune Tolerance.
LDR:04021nmm a2200397 4500 001 2282084
005 20210927083536.5
008 220723s2021 ||||||||||||||||| ||eng d
020 $a 9798515271459
035 $a (MiAaPQ)AAI28497369
035 $a AAI28497369
040 $a MiAaPQ $c MiAaPQ
100 1 $a Li, Yuan-Ping Peter. $0 (orcid)0000-0003-0914-322X $3 3560825
245 1 0 $a Local Administration of Biomaterials for Inducing Antigen-Specific Immune Tolerance.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 130 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-12, Section: B.
500 $a Advisor: Cheng, Hao.
502 $a Thesis (Ph.D.)--Drexel University, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a Current treatment options for autoimmune conditions most commonly employ the use of nonspecific immunosuppressive agents that have significant adverse side effects. Ideally, the goal of autoimmune therapies is to achieve lasting autoantigen-specific tolerance. Nanoparticle (NP)-based therapies have recently shown promise in several animal models, but unfortunately, none have yet been validated in humans, and a deeper understanding of how different nanomaterials affect tolerogenic pathways is still needed. In this thesis, immune system interactions with local subcutaneous administrations of different materials are studied in the context of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, with the ultimate goal of creating and optimizing treatments for autoimmunity.First, a simple subcutaneous injection of a nanoparticle fabricated from PLGA-PEG block copolymer containing only antigen was found to be sufficient to dramatically ameliorate EAE symptoms. The tolerogenic capability of this particle was surprising due to the lack of any tolerogenic drug and because previous studies using PLGA alone did not significantly ameliorate disease. Thus, it was hypothesized that intrinsic properties of PLGA-PEG facilitated tolerogenic responses in ways that other polymers do not. This provided the opportunity to directly compare the effects of PLGA-PEG, PLGA, and partial PLGA/PLGA-PEG nanoparticles on treating EAE and their in vitro and in vivo responses. PLGA-PEG-NPs ameliorated EAE in both an antigen- and material-specific manner. The particles also demonstrated decreased complement activation, increased spleen and lymph node localization, and decreased activation of co-stimulatory molecules in dendritic cells in vivo. Mice successfully treated with the PLGA-PEG-NPs exhibited decreased IL-17 inflammatory cytokine production in response to antigen restimulation ex vivo.In an effort to develop a platform to study local cell recruitment and to further improve tolerogenic responses, a macroporous alginate-based polymeric scaffold system was created. When incorporated with the cytokine GM-CSF, this system demonstrated the ability to recruit significant populations of dendritic cells in vivo, which are the most important cells in immunomodulation. The addition of antigen-loaded PLGA-PEG-NPs allowed the system to also reverse symptoms of EAE after the onset of disease. However, the scaffold system failed to demonstrate an improvement over PLGA-PEG-NPs alone. Overall, these studies will hopefully pave the way for future iterations of scaffold-based autoimmune treatments, a greater understanding of PLGA-based materials for inducing tolerance, and a promising and simple PLGA-PEG nanoparticle for treating autoimmunity.
590 $a School code: 0065.
650 4 $a Immunology. $3 611031
650 4 $a Bioengineering. $3 657580
650 4 $a Materials science. $3 543314
650 4 $a Microbiology. $3 536250
650 4 $a Nanoscience. $3 587832
653 $a Local administration
653 $a Biomaterials
653 $a Antigen-specific immune tolerance
653 $a Immunosuppressive agents
653 $a Nanoparticle-based therapies
690 $a 0982
690 $a 0202
690 $a 0794
690 $a 0410
690 $a 0565
710 2 $a Drexel University. $b Materials Science and Engineering (College of Engineering). $3 3168982
773 0 $t Dissertations Abstracts International $g 82-12B.
790 $a 0065
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28497369