PMID- 25152701 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211021 IS - 1550-7033 (Print) IS - 1550-7041 (Electronic) IS - 1550-7033 (Linking) VI - 4 IP - 4 DP - 2008 Dec 1 TI - Development of Receptor Targeted Magnetic Iron Oxide Nanoparticles for Efficient Drug Delivery and Tumor Imaging. PG - 439-449 AB - 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 (IO) 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 IO 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 IO nanoparticles. This class of Dox-loaded nanoparticles has a compact size and is stable in pH 7.4 buffer. However, encapsulated Doxcan 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 IO-Dox nanoparticles, uPAR-targeted IO-Dox nanoparticles deliver higher levels of Dox into breast cancer cells and produce a stronger inhibitory effect on tumor cell growth. Importantly, Dox-loaded IO 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. FAU - Yang, Lily AU - Yang L AD - Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA ; Radiology, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Cao, Zehong AU - Cao Z AD - Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Sajja, Hari Krishna AU - Sajja HK AD - Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Mao, Hui AU - Mao H AD - Radiology, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Wang, Liya AU - Wang L AD - Radiology, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Geng, Huaying AU - Geng H AD - Ocean Nanotech, LLC, 700 Research Center Blvd, 72701, Fayetteville, Arkansas, USA. FAU - Xu, Hengyi AU - Xu H AD - Ocean Nanotech, LLC, 700 Research Center Blvd, 72701, Fayetteville, Arkansas, USA. FAU - Jiang, Tieshan AU - Jiang T AD - Ocean Nanotech, LLC, 700 Research Center Blvd, 72701, Fayetteville, Arkansas, USA. FAU - Wood, William C AU - Wood WC AD - Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Nie, Shuming AU - Nie S AD - Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia, GA 30322, USA. FAU - Wang, Y Andrew AU - Wang YA AD - Ocean Nanotech, LLC, 700 Research Center Blvd, 72701, Fayetteville, Arkansas, USA. LA - eng GR - R01 CA163256/CA/NCI NIH HHS/United States GR - R01 CA133722/CA/NCI NIH HHS/United States GR - U54 CA119338/CA/NCI NIH HHS/United States GR - R01 CA133722-02/CA/NCI NIH HHS/United States GR - R01 CA154846/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - J Biomed Nanotechnol JT - Journal of biomedical nanotechnology JID - 101230869 PMC - PMC4139059 MID - NIHMS296607 OTO - NOTNLM OT - Breast Cancer OT - Doxorubicin OT - Drug Delivery Nanoparticle OT - Magnetic Iron Oxide Nanoparticles OT - Targeted Nanoparticle OT - uPAR EDAT- 2008/12/01 00:00 MHDA- 2008/12/01 00:01 PMCR- 2014/08/20 CRDT- 2014/08/26 06:00 PHST- 2014/08/26 06:00 [entrez] PHST- 2008/12/01 00:00 [pubmed] PHST- 2008/12/01 00:01 [medline] PHST- 2014/08/20 00:00 [pmc-release] AID - 10.1166/jbn.2008.007 [doi] PST - ppublish SO - J Biomed Nanotechnol. 2008 Dec 1;4(4):439-449. doi: 10.1166/jbn.2008.007.