Characterization of the intracellular dynamics of a non-degradative pathway accessed by polymer nanoparticles

Samuel K. Lai, Kaoru Hida, Clive Chen, Justin Hanes

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)107-111
Number of pages5
JournalJournal of Controlled Release
Volume125
Issue number2
DOIs
StatePublished - Jan 22 2008

Keywords

  • Confocal particle tracking
  • Endosomes
  • Microtubules
  • Transport

ASJC Scopus subject areas

  • Pharmaceutical Science

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