科研之友
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摘要
The development of multifunctional nanoparticles that have dual capabilities of tumor imaging and delivering therapeutic agents into tumor cells holds great promises for novel approaches for tumor imaging and therapy We have engineered urokinase plasminogen activator receptor (uPAR) targeted biodegradable nanoparticles using a size uniform and amphiphilic polymer-coated magnetic iron oxide (10) nanoparticle conjugated with the amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), which is a high affinity natural ligand for uPAR. We further developed methods to encapsulate hydrophobic chemotherapeutic drugs into the polymer layer on the 10 nanoparticles, making these targeted magnetic resonance imaging (MRI) sensitive nanoparticles drug delivery vehicles. Using a fluorescent drug doxorubicin (Dox) as a model system, we showed that this hydrophobic drug can be efficiently encapsulated into the uPAR-targeted 10 nanoparticles. This class of Dox-loaded nanoparticles has a compact size and is stable in pH 7.4 buffer. However, encapsulated Dox can be released from the nanoparticles at pH 4.0 to 5.0 within 2 hrs. In comparison with the effect of equivalent dosage of free drug or non-targeted 10-Dox nanoparticles, uPAR-targeted 10-Dox nanoparticles deliver higher levels of Dox into breast cancer cells and produce a stronger inhibitory effect on tumor cell growth. Importantly, Dox-loaded 10 nanoparticles maintain their T2 MRI contrast effect after being internalized into the tumor cells due to their significant susceptibility effect in the cells, indicating that this drug delivery nanoparticle has the potential to be used as targeted therapeutic imaging probes for monitoring the drug delivery using MRI.
- 出版日期2008-12
