Programmable multistage drug delivery to lymph nodes
| Autor: | Asheley P. Chapman, Cody J. Higginson, David M. Francis, Alex Schudel, Alexa Regina Chua Avecilla, M. G. Finn, Susan N. Thomas, Mei-Kwan Yau, Nathan A. Rohner, Margaret P. Manspeaker |
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| Rok vydání: | 2020 |
| Předmět: |
Lymphoma
Biomedical Engineering Bioengineering 02 engineering and technology Lymph Node Cortex 010402 general chemistry 01 natural sciences Article Cell Line Drug Delivery Systems Immune system Adjuvants Immunologic medicine Animals Humans General Materials Science Electrical and Electronic Engineering Lymph node Chemistry Node (networking) 021001 nanoscience & nanotechnology Condensed Matter Physics Controlled release Atomic and Molecular Physics and Optics 0104 chemical sciences Mice Inbred C57BL Lymphatic system medicine.anatomical_structure Oligodeoxyribonucleotides Delayed-Action Preparations Drug delivery Cancer research Nanoparticles Female Immunotherapy Lymph Nodes Lymph 0210 nano-technology |
| Zdroj: | Nature nanotechnology |
| ISSN: | 1748-3395 1748-3387 |
| DOI: | 10.1038/s41565-020-0679-4 |
| Popis: | Therapeutic delivery selectively to lymph nodes has the potential to address a variety of unmet clinical needs. However, owing to the unique structure of the lymphatics and the size-restrictive nature of the lymph node reticular network, delivering cargo to specific cells in the lymph node cortex and paracortex is difficult. Here, we describe a delivery system to overcome lymphatic and intra-lymph node transport barriers by combining nanoparticles that are rapidly conveyed to draining lymph nodes after administration in peripheral tissues with programmable degradable linkers. This platform enables the controlled release of intra-lymph-mobile small-molecular cargo, which can reach vastly more immune cells throughout the lymph node than either the particles or free compounds alone. The release rate can be programmed, allowing access to different lymph node structures and therefore specific lymphocyte subpopulations. We are thus able to alter the subtypes of drugged lymph node cells to improve immunotherapeutic effects. Nanoparticles that access lymphatic vessels and are functionalized with degradable linkers, whose half-lives can be programmed, enable the controlled release of therapeutic cargo in different regions of the lymph nodes, allowing the targeting of otherwise difficult-to-reach lymphocyte subpopulations. |
| Databáze: | OpenAIRE |
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