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Chitosan Nanoparticles for Nuclear Targeting: The Effect of Nanoparticle Size and Nuclear Localization Sequence Density.

Many recently discovered therapeutic proteins exert their main function in the nucleus, thus requiring both efficient uptake and correct intracellular targeting. Chitosan nanoparticles (NPs) have attracted interest as protein delivery vehicles due to their biocompatibility and ability to escape the... Full description

Journal Title: Molecular pharmaceutics December 7, 2015, Vol.12(12), pp.4277-4289
Main Author: Tammam, Salma N
Other Authors: Azzazy, Hassan M E , Breitinger, Hans G , Lamprecht, Alf
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1543-8392 ; DOI: 10.1021/acs.molpharmaceut.5b00478
Link: http://search.proquest.com/docview/1746870518/?pq-origsite=primo
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recordid: proquest1746870518
title: Chitosan Nanoparticles for Nuclear Targeting: The Effect of Nanoparticle Size and Nuclear Localization Sequence Density.
format: Article
creator:
  • Tammam, Salma N
  • Azzazy, Hassan M E
  • Breitinger, Hans G
  • Lamprecht, Alf
subjects:
  • Animals–Metabolism
  • Cell Line–Drug Effects
  • Cell Nucleus–Administration & Dosage
  • Cell Survival–Chemistry
  • Chitosan–Administration & Dosage
  • Drug Carriers–Chemistry
  • Endosomes–Metabolism
  • Mice–Administration & Dosage
  • Nanoparticles–Chemistry
  • Nuclear Localization Signals–Administration & Dosage
  • Particle Size–Chemistry
  • Drug Carriers
  • Nuclear Localization Signals
  • Chitosan
  • Fret
  • Active Targeting
  • Chitosan Nanoparticles
  • Nuclear Delivery
  • Nuclear Localization Sequence
  • Nuclear Localization Sequence Density
  • Nuclear Targeting
  • Protein Delivery
ispartof: Molecular pharmaceutics, December 7, 2015, Vol.12(12), pp.4277-4289
description: Many recently discovered therapeutic proteins exert their main function in the nucleus, thus requiring both efficient uptake and correct intracellular targeting. Chitosan nanoparticles (NPs) have attracted interest as protein delivery vehicles due to their biocompatibility and ability to escape the endosomes offering high potential for nuclear delivery. Molecular entry into the nucleus occurs through the nuclear pore complexes, the efficiency of which is dependent on NP size and the presence of nuclear localization sequence (NLS). Chitosan nanoparticles of different sizes (S-NPs ≈ 25 nm; L-NP ≈ 150 nm) were formulated, and they were modified with different densities of the octapeptide NLS CPKKKRKV (S-NPs, 0.25, 0.5, 2.0 NLS/nm(2); L-NPs, 0.6, 0.9, 2 NLS/nm(2)). Unmodified and NLS-tagged NPs were evaluated for their protein loading capacity, extent of cell association, cell uptake, cell surface binding, and finally nuclear delivery efficiency in L929 fibroblasts. To avoid errors generated...
language: eng
source:
identifier: E-ISSN: 1543-8392 ; DOI: 10.1021/acs.molpharmaceut.5b00478
fulltext: fulltext
issn:
  • 15438392
  • 1543-8392
url: Link


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titleChitosan Nanoparticles for Nuclear Targeting: The Effect of Nanoparticle Size and Nuclear Localization Sequence Density.
creatorTammam, Salma N ; Azzazy, Hassan M E ; Breitinger, Hans G ; Lamprecht, Alf
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ispartofMolecular pharmaceutics, December 7, 2015, Vol.12(12), pp.4277-4289
identifierE-ISSN: 1543-8392 ; DOI: 10.1021/acs.molpharmaceut.5b00478
subjectAnimals–Metabolism ; Cell Line–Drug Effects ; Cell Nucleus–Administration & Dosage ; Cell Survival–Chemistry ; Chitosan–Administration & Dosage ; Drug Carriers–Chemistry ; Endosomes–Metabolism ; Mice–Administration & Dosage ; Nanoparticles–Chemistry ; Nuclear Localization Signals–Administration & Dosage ; Particle Size–Chemistry ; Drug Carriers ; Nuclear Localization Signals ; Chitosan ; Fret ; Active Targeting ; Chitosan Nanoparticles ; Nuclear Delivery ; Nuclear Localization Sequence ; Nuclear Localization Sequence Density ; Nuclear Targeting ; Protein Delivery
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descriptionMany recently discovered therapeutic proteins exert their main function in the nucleus, thus requiring both efficient uptake and correct intracellular targeting. Chitosan nanoparticles (NPs) have attracted interest as protein delivery vehicles due to their biocompatibility and ability to escape the endosomes offering high potential for nuclear delivery. Molecular entry into the nucleus occurs through the nuclear pore complexes, the efficiency of which is dependent on NP size and the presence of nuclear localization sequence (NLS). Chitosan nanoparticles of different sizes (S-NPs ≈ 25 nm; L-NP ≈ 150 nm) were formulated, and they were modified with different densities of the octapeptide NLS CPKKKRKV (S-NPs, 0.25, 0.5, 2.0 NLS/nm(2); L-NPs, 0.6, 0.9, 2 NLS/nm(2)). Unmodified and NLS-tagged NPs were evaluated for their protein loading capacity, extent of cell association, cell uptake, cell surface binding, and finally nuclear delivery efficiency in L929 fibroblasts. To avoid errors generated...
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