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The intranuclear release of a potential anticancer drug from small nanoparticles that are derived from intracellular dissociation of large nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
7308 544 2012 9 PDF Available
Title
The intranuclear release of a potential anticancer drug from small nanoparticles that are derived from intracellular dissociation of large nanoparticles
Abstract

Transporting drug-containing nanoparticles into the nucleus of cancer cells through nucleopores and then releasing the drug intranuclearly provide an efficient strategy to overcome the drug resistance mechanisms evolved by cancer cells. However, limited by the diameter of nucleopores, nanoparticles capable of going through nucleopores should be small enough, whereas the nanoparticles with the small size may have short circulation time in blood and low accumulation in solid tumors. We solved this dilemma successfully by preparing kinetically frozen large compound nanoparticles (sized 128 nm) of complex of oligolysine/iridium(III) compound (a potential anticancer drug) that can dissociate into small ones in lysosome environment. The small nanoparticles retain their small size in cytosol after escaping from the lysosomes, so that they can enter the nucleus actively through nucleaopores, with the help of oligolysine segments on the surfaces of nanoparticles acting as the nuclear targeting moieties. It is significant that the nanoparticles can release the contained Ir compound within the nucleus. Further study reveals that the release is triggered by DNA interaction with the nanoparticles, which is responsible for the observation that the release occurs only in the nucleus. We believe that the present study, representing the first example of DNA triggered intranuclear release from nanoparticles, will provide a promising pathway for chemotherapy.

Keywords
Iridium; Polymeric nanoparticle; Drug resistance; Nanoparticle nuclear entry; Intranuclear drug release; DNA
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The intranuclear release of a potential anticancer drug from small nanoparticles that are derived from intracellular dissociation of large nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 16, June 2012, Pages 4220–4228
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us