Characterization of the intracellular dynamics of a non-degradative pathway accessed by polymer nanoparticles.
Recently, 24 nm polymer nanoparticles were found to access a privileged non-degradative intracellular pathway that leads to perinuclear accumulation. Here, we report the intracellular dynamics of vesicles containing polymer nanoparticles within this non-degradative pathway, characterized by clathrin- and caveolae-independent endocytosis, as compared to endosomes originating from classical clathrin-mediated endocytosis. Similar to transport of acidic endosomes and lysosomes, the dynamic movements of non-degradative vesicles exhibit substantial heterogeneity, including caged diffusion and pearls-on-a-string trajectories, a reflection of microtubule-dependent active transport that leads to rapid accumulation near the cell nucleus. However, the ensemble-averaged intracellular transport rate of vesicles in the non-degradative pathway is 4-fold slower than that of the acidic vesicles of late endosomes and lysosomes, highlighted by a 3-fold smaller fraction of actively transported vesicles. The distinct intracellular dynamics further confirms that small nanoparticles are capable of entering cells via a distinct privileged pathway that does not lead to lysosomal processing. This non-degradative pathway may prove beneficial for the delivery of therapeutics and nucleic acids to the nucleus or nearby organelles.
Department of Chemical & Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Samuel K
SK
Lai
Kaoru
K
Hida
Clive
C
Chen
Justin
J
Hanes
D001692:Biological Transport; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles; D011108:Polymers
D002966:Clathrin; D011108:Polymers