Modifying a Commonly Expressed Endocytic Receptor
Retargets Nanoparticles in Vivo
Version 2 2018-09-20, 18:52
Version 1 2018-09-20, 18:48
Posted on 2018-09-20 - 18:52
Nanoparticles
are often targeted to receptors expressed on specific
cells, but few receptors are (i) highly expressed on one cell type
and (ii) involved in endocytosis. One unexplored alternative is manipulating
an endocytic gene expressed on multiple cell types; an ideal gene
would inhibit delivery to cell type A more than cell type B, promoting
delivery to cell type B. This would require a commonly expressed endocytic
gene to alter nanoparticle delivery in a cell type-dependent manner
in vivo; whether this can occur is unknown. Based on its microenvironmental
regulation, we hypothesized Caveolin 1 (Cav1) would exert cell type-specific
effects on nanoparticle delivery. Fluorescence was not sensitive enough
to investigate this question, and as a result, we designed a platform
named QUANT to study nanoparticle biodistribution. QUANT is 108× more sensitive than fluorescence and can be multiplexed. By measuring
how 226 lipid nanoparticles (LNPs) delivered nucleic acids to multiple
cell types in vivo in wild-type and Cav1 knockout mice, we found Cav1
altered delivery in a cell-type specific manner. Cav1 knockout did
not alter LNP delivery to lung and kidney macrophages but substantially
reduced LNP delivery to Kupffer cells, which are liver-resident macrophages.
These data suggest caveolin-mediated endocytosis of nanomedicines
by macrophages varies with tissue type. These results suggest manipulating
receptors expressed on multiple cell types can tune drug delivery.
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Sago, Cory D.; Lokugamage, Melissa P.; Lando, Gwyneth N.; Djeddar, Naima; Shah, Nirav N.; Syed, Chris; et al. (2018). Modifying a Commonly Expressed Endocytic Receptor
Retargets Nanoparticles in Vivo. ACS Publications. Collection. https://doi.org/10.1021/acs.nanolett.8b03149
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AUTHORS (8)
CS
Cory D. Sago
ML
Melissa P. Lokugamage
GL
Gwyneth N. Lando
ND
Naima Djeddar
NS
Nirav N. Shah
CS
Chris Syed
AV
Anton V. Bryksin
JD
James E. Dahlman