Open AccessProgrammable multistage drug delivery to lymph nodes
Author(s) -
Alex Schudel,
Asheley Poole Chapman,
Mei-Kwan Yau,
Cody J. Higginson,
David M. Francis,
Margaret P. Manspeaker,
Alexa Regina Chua Avecilla,
Nathan A. Rohner,
M. G. Finn,
Susan N. Thomas
Publication year - 2020
Publication title -
nature nanotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.308
H-Index - 353
eISSN - 1748-3395
pISSN - 1748-3387
DOI - 10.1038/s41565-020-0679-4
Subject(s) - lymph node , lymph , reticular cell , lymphatic system , lymph node stromal cell , drug delivery , node (physics) , immune system , computer science , medicine , pathology , immunology , nanotechnology , spleen , materials science , physics , quantum mechanics
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.