Programmable multistage drug delivery to lymph nodes
Open Access
- 1 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Nanotechnology
- Vol. 15 (6), 491-499
- https://doi.org/10.1038/s41565-020-0679-4
Abstract
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.Funding Information
- American Heart Association
- National Science Foundation (CHE 1011796)
- U.S. Department of Health & Human Services | National Institutes of Health (T32EB021962, T32GM008433, R01CA207619)
- Georgia Tech | Parker H. Petit Institute for Bioengineering and Bioscience
- Georgia CORE/It's the Journey
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