Adoptive Macrophage Transfers for Nanoparticle Delivery

用于纳米颗粒递送的过继巨噬细胞转移

• 批准号: 10794553
• 负责人: Charles Wyatt Shields IV
• 金额: $ 18.06万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10794553
• 关键词: Address; Adoptive Transfer; Affect; Area; Autoimmune Diseases; Behavior; Cardiovascular Diseases; Cell surface; Cells; Clinical; Communicable Diseases; Complex; Contrast Media; Disease; Drug Delivery Systems; Genes; Goals; Immune; Infiltration; Inflammation; Inflammatory; Knowledge; Laboratories; Macrophage; Malignant Neoplasms; Measures; Mediating; Medical Imaging; Modeling; Mus; Outcome; Pharmaceutical Preparations; Phenotype; Research Personnel; Role; Shapes; Site; Specificity; Tissues; Vaccines; Work; chemokine receptor; design; differential expression; epigenomics; improved; molecular phenotype; nanofabrication; nanoparticle; nanoparticle delivery; next generation; physical property; recruit; response; tool; transcriptomics

ABSTRACT Immune cells will serve as next-generation vehicles to deliver cargo such as bioactive drugs and contrast agents to inflamed tissues. Due to their abundant expression of chemokine receptors, cells like macrophages have the capacity to infiltrate inflamed tissues with remarkable specificity. Researchers are exploiting this capability to direct the transport of attached nanoparticles containing drugs and other cargo to diseased tissues (e.g., from cancer, infectious diseases, autoimmune disorders, and cardiovascular disease). However, macrophages are living entities that can change their function in complex and sometimes unexpected ways when loaded with nanoparticles. Thus, there is a fundamental need to understand the interactions between macrophages and the nanoparticles they carry. To address this gap in knowledge, my laboratory will investigate two focus areas. First, we will study how the physical properties of nanoparticles affect macrophage phenotypes. Using nanofabrication, we will create nanoparticles that vary in size, shape, stiffness, and composition; direct their attachment onto, or internalization within, macrophages; and measure their responses using epigenomic, transcriptomic, and molecular phenotyping tools. This focus area will reveal differentially expressed genes that are involved in the macrophage responses to nanoparticle loadings of various design. In the second focus area, we will study the principal factors that govern cell-mediated transport of nanoparticles to inflamed tissues. Different macrophage- nanoparticle complexes will be made and injected into mice harboring different models of inflammation designed to recruit different subpopulations of immune cells. We will study the role of nanoparticle placement (i.e., onto the surfaces of cells versus within their interiors) as well as the role of macrophage phenotypes on their transport efficiency to inflamed tissues. The outcome of this work will be a set of design rules that predict macrophage- mediated transport of nanoparticles to inflamed tissues. Once established, these rules will be exploited to guide the design of new types of nanoparticles that interface with macrophages, promote specific phenotypes that are advantageous for specific treatments, and facilitate improved transport to those diseased sites. Such a capability will improve clinical efforts to use adoptively transferred macrophages to deliver drugs, vaccines, and contrast agents for a range of inflammatory diseases.

摘要

项目成果

Systemic Tumor Suppression via Macrophage-Driven Automated Homing of Metal-Phenolic-Gated Nanosponges for Metastatic Melanoma.

• DOI: 10.1002/advs.202207488
• 发表时间: 2023-06
• 期刊: ADVANCED SCIENCE
• 影响因子: 15.1
• 作者: Liao, Xue;Gong, Guidong;Dai, Mengyuan;Xiang, Zhenyu;Pan, Jiezhou;He, Xianglian;Shang, Jiaojiao;Blocki, Anna Maria;Zhao, Zongmin;Shields IV, C. Wyatt;Guo, Junling
• 通讯作者: Guo, Junling

Microrobots for Biomedicine: Unsolved Challenges and Opportunities for Translation

• DOI: 10.1021/acsnano.3c03723
• 发表时间: 2023-07-26
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Lee, Jin Gyun;Raj, Ritu R.;Shields, C. Wyatt
• 通讯作者: Shields, C. Wyatt