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J Control Release. 2004 Jun 18;97(2):345-56.

Block copolymer-coated calcium phosphate nanoparticles sensing intracellular environment for oligodeoxynucleotide and siRNA delivery.

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  • 1Biomaterials Center, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

Abstract

The organic-inorganic hybrid nanoparticles entrapping oligodeoxynucleotide (ODN) or siRNA were prepared through the self-associating phenomenon of the block copolymer, poly(ethylene glycol)-block-poly(aspartic acid) (PEG-PAA), with calcium phosphate. The nanoparticles have diameters in the range of several hundreds of nanometers depending on the PEG-PAA concentration and revealed excellent colloidal stability due to the steric repulsion effect of the PEG layer surrounding the calcium phosphate core. The loading capacities of ODN and siRNA were fairly high, reaching almost 100% under optimal conditions. The flowcytometric analysis and confocal microscopy observation indicated that the hybrid nanoparticles loaded with ODN were taken up by the cells through the endocytosis mechanism. Furthermore, the calcium phosphate core dissociates in the intracellular environment with appreciably lowered calcium ion concentration compared to the exterior, allowing the release of the incorporated ODN and siRNA in a controlled manner. Eventually, effective intracellular delivery and nuclear localization of these nucleic acid-based drugs were evidenced through the observation of laser confocal microscopy using FITC-labeled ODN. This smart ion-sensitive characteristic of hybrid nanoparticles was further demonstrated by the appreciable silencing of reporter gene expression by siRNA incorporated in the nanoparticles.

Copyright 2004 Elsevier B.V.

PMID:
15196761
[PubMed - indexed for MEDLINE]
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