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The Potential of Nanoparticle-Mediated Macrophage Polarization for Solid Tumor Therapy: Evidence Synthesis and Temporal Monitoring
The Potential of Nanoparticle-Mediated Macrophage Polarization for Solid Tumor Therapy: Evidence Synthesis and Temporal Monitoring
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151149
- ISBN
- 9798382310176
- DDC
- 610
- 서명/저자
- The Potential of Nanoparticle-Mediated Macrophage Polarization for Solid Tumor Therapy: Evidence Synthesis and Temporal Monitoring
- 발행사항
- [Sl] : Carnegie Mellon University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 215 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-10, Section: B.
- 주기사항
- Advisor: Wayne, Elizabeth C.
- 학위논문주기
- Thesis (Ph.D.)--Carnegie Mellon University, 2024.
- 초록/해제
- 요약Cancer persists as a significant public health challenge despite treatment advances. Colorectal cancer is especially a concern because its incidence and mortality are increasing in young individuals. Solid tumors, such as colorectal cancer, are challenging to treat with immunotherapies due to their immunosuppressive microenvironment preventing T cell infiltration. Tumor-associated macrophages (TAMs) play a pivotal role in supporting this immunosuppression by adopting an anti-inflammatory and pro-tumoral phenotype within the tumor microenvironment. Leveraging nanoparticles to repolarize TAMs towards a proinflammatory and tumoricidal phenotype holds promise for solid tumor therapy. However, clinical translation of cancer nanomedicines has been slow. This dissertation aims to address this through quantitative review of the intersection between the colorectal cancer nanomedicine and macrophage polarization, and by proposing a novel method of temporally tracking macrophage polarization using bioluminescent reporter cells.Using eLDA topic modeling, the dissertation identifies six major topics in the intersection of cancer medicine and macrophage polarization, providing insights into nanoparticle design choices and therapeutic strategies across various cancer types. A scoping review and meta-analysis of colorectal cancer nanomedicine over two decades reveal evolving nanoparticle design strategies and their impact on macrophage polarization. We also demonstrate how a nanoparticle's ability to increase macrophages' ratio of M1 to M2 polarization is correlated with their efficacy at reducing tumor growth and increasing survival. This dissertation also includes a technology assessment of how evidence synthesis of preclinical studies informs open science policy.To better temporally track macrophage polarization, the dissertation introduces a method utilizing THP-1 reporter cells with bioluminescently labeled polarization-relevant transcription factors. We demonstrated how these reporter cells enable time-resolved activation curves for tumor-associated macrophages, revealing unique NFκB activation profiles dependent on cancer type that we linked to the tumor microenvironments immunogenicity. Furthermore, monitoring monocyte to macrophage differentiation with this method highlights the importance of selecting appropriate differentiation protocols for the intended use. These examples demonstrate the potential use of this bioluminescent platform to monitor macrophage polarization in response to immunomodulatory treatments, like macrophage-targeted cancer nanomedicine.
- 일반주제명
- Biomedical engineering
- 일반주제명
- Public health
- 일반주제명
- Oncology
- 일반주제명
- Nanoscience
- 키워드
- Macrophage
- 키워드
- Nanomedicine
- 키워드
- Nanoparticles
- 키워드
- Polarization
- 기타저자
- Carnegie Mellon University Biomedical Engineering
- 기본자료저록
- Dissertations Abstracts International. 85-10B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151149
■006m o d
■007cr#unu||||||||
■020 ▼a9798382310176
■035 ▼a(MiAaPQ)AAI31235326
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a610
■1001 ▼aBilynsky, Colette Sandra Macedo.▼0(orcid)0000-0002-7865-195X
■24510▼aThe Potential of Nanoparticle-Mediated Macrophage Polarization for Solid Tumor Therapy: Evidence Synthesis and Temporal Monitoring
■260 ▼a[Sl]▼bCarnegie Mellon University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a215 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-10, Section: B.
■500 ▼aAdvisor: Wayne, Elizabeth C.
■5021 ▼aThesis (Ph.D.)--Carnegie Mellon University, 2024.
■520 ▼aCancer persists as a significant public health challenge despite treatment advances. Colorectal cancer is especially a concern because its incidence and mortality are increasing in young individuals. Solid tumors, such as colorectal cancer, are challenging to treat with immunotherapies due to their immunosuppressive microenvironment preventing T cell infiltration. Tumor-associated macrophages (TAMs) play a pivotal role in supporting this immunosuppression by adopting an anti-inflammatory and pro-tumoral phenotype within the tumor microenvironment. Leveraging nanoparticles to repolarize TAMs towards a proinflammatory and tumoricidal phenotype holds promise for solid tumor therapy. However, clinical translation of cancer nanomedicines has been slow. This dissertation aims to address this through quantitative review of the intersection between the colorectal cancer nanomedicine and macrophage polarization, and by proposing a novel method of temporally tracking macrophage polarization using bioluminescent reporter cells.Using eLDA topic modeling, the dissertation identifies six major topics in the intersection of cancer medicine and macrophage polarization, providing insights into nanoparticle design choices and therapeutic strategies across various cancer types. A scoping review and meta-analysis of colorectal cancer nanomedicine over two decades reveal evolving nanoparticle design strategies and their impact on macrophage polarization. We also demonstrate how a nanoparticle's ability to increase macrophages' ratio of M1 to M2 polarization is correlated with their efficacy at reducing tumor growth and increasing survival. This dissertation also includes a technology assessment of how evidence synthesis of preclinical studies informs open science policy.To better temporally track macrophage polarization, the dissertation introduces a method utilizing THP-1 reporter cells with bioluminescently labeled polarization-relevant transcription factors. We demonstrated how these reporter cells enable time-resolved activation curves for tumor-associated macrophages, revealing unique NFκB activation profiles dependent on cancer type that we linked to the tumor microenvironments immunogenicity. Furthermore, monitoring monocyte to macrophage differentiation with this method highlights the importance of selecting appropriate differentiation protocols for the intended use. These examples demonstrate the potential use of this bioluminescent platform to monitor macrophage polarization in response to immunomodulatory treatments, like macrophage-targeted cancer nanomedicine.
■590 ▼aSchool code: 0041.
■650 4▼aBiomedical engineering
■650 4▼aPublic health
■650 4▼aOncology
■650 4▼aNanoscience
■653 ▼aColorectal cancer
■653 ▼aEvidence synthesis
■653 ▼aMacrophage
■653 ▼aNanomedicine
■653 ▼aNanoparticles
■653 ▼aPolarization
■690 ▼a0541
■690 ▼a0565
■690 ▼a0992
■690 ▼a0573
■71020▼aCarnegie Mellon University▼bBiomedical Engineering.
■7730 ▼tDissertations Abstracts International▼g85-10B.
■790 ▼a0041
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161010▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
