Targeting of nanoparticles to the clathrin-mediated endocytic pathway.
Nanoparticles (NPs) are considered attractive carriers for gene therapy and drug delivery owing to their minor toxic effect and their ability to associate and internalize into mammalian cells. In this study, we compared the endocytosis into HeLa cells of NPs exposing either a negative or positive charge on their surface. The exposed charge significantly affected their ability to internalize as well as the cellular endocytosis mechanism utilized. Negatively charged NPs show an inferior rate of endocytosis and do not utilize the clathrin-mediated endocytosis pathway. On the other hand, positively charged NPs internalize rapidly via the clathrin-mediated pathway. When this pathway is blocked, NPs activate a compensatory endocytosis pathway that results in even higher accumulation of NPs. Overall, the addition of a positive charge to NPs may improve their potential as nanoparticulate carriers for drug delivery.
Harush-Frenkel
Oshrat
O
Departments of Pharmaceutics, The School of Pharmacy, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
Debotton
Nir
N
Benita
Simon
S
Altschuler
Yoram
Y
D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002966:Clathrin / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects*
D001672:Biocompatible Materials; D002966:Clathrin