TY - JOUR
T1 - Characterization of the intracellular dynamics of a non-degradative pathway accessed by polymer nanoparticles
AU - Lai, Samuel K.
AU - Hida, Kaoru
AU - Chen, Clive
AU - Hanes, Justin
N1 - Funding Information:
We thank the Integrated Imaging Center at Johns Hopkins University. We acknowledge financial support from the National Science Foundation (NSF 0346716), from the National Institutes of Health (NIH1R01EB003558-01), from the Natural Science & Engineering Research Council of Canada (PGSD for S.K.L.), and Office of the Provost of the Johns Hopkins University (PURA for C.C.).
PY - 2008/1/22
Y1 - 2008/1/22
N2 - 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.
AB - 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.
KW - Confocal particle tracking
KW - Endosomes
KW - Microtubules
KW - Transport
UR - http://www.scopus.com/inward/record.url?scp=37349037137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37349037137&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2007.10.015
DO - 10.1016/j.jconrel.2007.10.015
M3 - Article
C2 - 18053606
AN - SCOPUS:37349037137
SN - 0168-3659
VL - 125
SP - 107
EP - 111
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -