Related Experiment Video
Updated: May 1, 2026
09:52
Non-invasive Optical Imaging of the Lymphatic Vasculature of a Mouse
Published on: March 8, 2013
16.2K
Three-Dimensional Lymphatics-on-a-Chip Reveals Distinct, Size-Dependent Nanoparticle Transport Mechanisms in
Renhao Lu1, Benjamin J Lee1, Esak Lee1
1Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States.
ACS Biomaterials Science & Engineering
|August 23, 2024
Summary
Smaller nanoparticles (30-50 nm) accumulate in cells, delaying lymphatic transport, unlike larger ones. Dynamin inhibition enhances small nanoparticle delivery, revealing size-dependent mechanisms for improved lymphatic drug delivery.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery
Background:
- Nanoparticle-based lymphatic drug delivery shows promise for various diseases.
- Clinical translation is hindered by low efficiency and unclear transport mechanisms.
Purpose of the Study:
- To investigate the size-dependent transport mechanisms of nanoparticles in lymphatic vessels.
- To identify strategies for enhancing nanoparticle lymphatic drug delivery.
Main Methods:
- Utilized a 3D lymphatics-on-a-chip model with engineered lymphatic vessels.
- Tested PLGA-b-PEG nanoparticles (30, 50, 70 nm) and employed endocytosis/transport inhibitors (dynasore, nystatin, amiloride, adrenomedullin).
Main Results:
- Smaller NPs (30, 50 nm) showed faster interstitial transport but were delayed by cytosolic accumulation in lymphatic endothelial cells (LECs).
- Dynamin inhibition enhanced smaller NP transport; caveolin inhibition affected larger NP transport, indicating distinct endocytosis pathways.
- Paracellular transport inhibition blocked all NP sizes, while macropinocytosis inhibition had no effect.
- Smaller NPs accumulated in Rab7-positive endosomes, delaying drainage, which was reversed by dynamin inhibition.
Conclusions:
- Unveiled distinct, size-dependent nanoparticle transport mechanisms within lymphatic vessels.
- Identified dynamin and Rab7 as potential targets to improve lymphatic delivery of smaller nanoparticles.
- The 3D lymphatics-on-a-chip model is a valuable tool for studying nanoparticle lymphatic transport.
Keywords:
caveolindrug deliverydynaminendocytosisintracellularlymphaticsmicrofluidicsnanoparticleparacellular
