Stiffness of targeted layer-by-layer nanoparticles impacts elimination half-life, tumor accumulation, and tumor penetration
Name
pnas.2104826118.pdf
Description
Published version
Size
1.42 MB
Format
Adobe PDF
Checksum (MD5)
7648bcbf223d2cbe7051f7659680c4e0
Author(s)
Kong, Stephanie M
Costa, Daniel F
Jagielska, Anna
Van Vliet, Krystyn J
Hammond, Paula T
Date Issued
2021
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Citation
Kong, Stephanie M, Costa, Daniel F, Jagielska, Anna, Van Vliet, Krystyn J and Hammond, Paula T. 2021. "Stiffness of targeted layer-by-layer nanoparticles impacts elimination half-life, tumor accumulation, and tumor penetration." Proceedings of the National Academy of Sciences of the United States of America, 118 (42).
Version
Final published version
Abstract
Significance
Layer-by-layer nanoparticles (LbL NPs), comprised of a charged core substrate layered sequentially with oppositely charged polyelectrolytes, are a promising class of drug delivery carriers for cancer therapeutics with demonstrated success in lowering off-target toxicity and enhancing efficacy. However, little is known about how LbL NP stiffness alters trafficking and delivery. Herein, we report that the stiffness of targeted LbL NPs, comprised of a liposome core and tumor-targeting, polymeric outer layers, can be tuned by altering the mechanical properties of its underlying liposomal core. We also show that these changes have a significant impact on in vivo NP trafficking properties; compliant LbL NPs have longer elimination times, higher organ and tumor accumulation, and higher tumor penetration.
Layer-by-layer nanoparticles (LbL NPs), comprised of a charged core substrate layered sequentially with oppositely charged polyelectrolytes, are a promising class of drug delivery carriers for cancer therapeutics with demonstrated success in lowering off-target toxicity and enhancing efficacy. However, little is known about how LbL NP stiffness alters trafficking and delivery. Herein, we report that the stiffness of targeted LbL NPs, comprised of a liposome core and tumor-targeting, polymeric outer layers, can be tuned by altering the mechanical properties of its underlying liposomal core. We also show that these changes have a significant impact on in vivo NP trafficking properties; compliant LbL NPs have longer elimination times, higher organ and tumor accumulation, and higher tumor penetration.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1073/PNAS.2104826118
