jz5b01739_si_001.pdf (2.4 MB)
Clathrin to Lipid Raft-Endocytosis via Controlled Surface Chemistry and Efficient Perinuclear Targeting of Nanoparticle
journal contribution
posted on 2015-12-17, 09:43 authored by Atanu Chakraborty, Nikhil R. JanaNanoparticle
interacts with live cells depending on their surface
chemistry, enters into cell via endocytosis, and is commonly trafficked
to an endosome/lysozome that restricts subcellular targeting options.
Here we show that nanoparticle surface chemistry can be tuned to alter
their cell uptake mechanism and subcellular trafficking. Quantum dot
based nanoprobes of 20–30 nm hydrodynamic diameters have been
synthesized with tunable surface charge (between +15 mV to −25
mV) and lipophilicity to influence their cellular uptake processes
and subcellular trafficking. It is observed that cationic nanoprobe
electrostatically interacts with cell membrane and enters into cell
via clathrin-mediated endocytosis. At lower surface charge (between
+10 mV to −10 mV), the electrostatic interaction with cell
membrane becomes weaker, and additional lipid raft endocytosis is
initiated. If a lipophilic functional group is introduced on a weakly
anionic nanoparticle surface, the uptake mechanism shifts to predominant
lipid raft-mediated endocytosis. In particular, the zwitterionic–lipophilic
nanoprobe has the unique advantage as it weakly interacts with anionic
cell membrane, migrates toward lipid rafts for interaction through
lipophilic functional group, and induces lipid raft-mediated endocytosis.
While predominate or partial clathrin-mediated entry traffics most
of the nanoprobes to lysozome, predominate lipid raft-mediated entry
traffics them to perinuclear region, particularly to the Golgi apparatus.
This finding would guide in designing appropriate nanoprobe for subcellular
targeting and delivery.