PMID- 23402593
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20221207
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Print)
IS  - 1936-0851 (Linking)
VI  - 7
IP  - 3
DP  - 2013 Mar 26
TI  - Theranostic nanoparticles with controlled release of gemcitabine for targeted 
      therapy and MRI of pancreatic cancer.
PG  - 2078-89
LID - 10.1021/nn3043463 [doi]
AB  - The tumor stroma in human cancers significantly limits the delivery of 
      therapeutic agents into cancer cells. To develop an effective therapeutic 
      approach overcoming the physical barrier of the stroma, we engineered urokinase 
      plasminogen activator receptor (uPAR)-targeted magnetic iron oxide nanoparticles 
      (IONPs) carrying chemotherapy drug gemcitabine (Gem) for targeted delivery into 
      uPAR-expressing tumor and stromal cells. The uPAR-targeted nanoparticle 
      construct, ATF-IONP-Gem, was prepared by conjugating IONPs with the 
      amino-terminal fragment (ATF) peptide of the receptor-binding domain of uPA, a 
      natural ligand of uPAR, and Gem via a lysosomally cleavable tetrapeptide linker. 
      These theranostic nanoparticles enable intracellular release of Gem following 
      receptor-mediated endocytosis of ATF-IONP-Gem into tumor cells and also provide 
      contrast enhancement in magnetic resonance imaging (MRI) of tumors. Our results 
      demonstrated the pH- and lysosomal enzyme-dependent release of gemcitabine, 
      preventing the drug from enzymatic degradation. Systemic administrations of 
      ATF-IONP-Gem significantly inhibited the growth of orthotopic human pancreatic 
      cancer xenografts in nude mice. With MRI contrast enhancement by IONPs, we 
      detected the presence of IONPs in the residual tumors following the treatment, 
      suggesting the possibility of monitoring drug delivery and assessing 
      drug-resistant tumors by MRI. The theranostic ATF-IONP-Gem nanoparticle has great 
      potential for the development of targeted therapeutic and imaging approaches that 
      are capable of overcoming the tumor stromal barrier, thus enhancing the 
      therapeutic effect of nanoparticle drugs on pancreatic cancers.
FAU - Lee, Gee Young
AU  - Lee GY
AD  - Departments of Surgery, Emory University School of Medicine, Atlanta, Georgia 
      30322, United States.
FAU - Qian, Wei Ping
AU  - Qian WP
FAU - Wang, Liya
AU  - Wang L
FAU - Wang, Yongqiang Andrew
AU  - Wang YA
FAU - Staley, Charles A
AU  - Staley CA
FAU - Satpathy, Minati
AU  - Satpathy M
FAU - Nie, Shuming
AU  - Nie S
FAU - Mao, Hui
AU  - Mao H
FAU - Yang, Lily
AU  - Yang L
LA  - eng
GR  - U01 CA151810/CA/NCI NIH HHS/United States
GR  - R01 CA163256/CA/NCI NIH HHS/United States
GR  - P50CA128301/CA/NCI NIH HHS/United States
GR  - R01 CA154129/CA/NCI NIH HHS/United States
GR  - R01CA154846/CA/NCI NIH HHS/United States
GR  - R01CA154129A01/CA/NCI NIH HHS/United States
GR  - U01CA151810/CA/NCI NIH HHS/United States
GR  - U54 CA119338/CA/NCI NIH HHS/United States
GR  - R01 CA154846/CA/NCI NIH HHS/United States
GR  - P50 CA128301/CA/NCI NIH HHS/United States
GR  - RC2 CA148265/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130312
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Magnetite Nanoparticles)
RN  - 0 (Nanocapsules)
RN  - 0W860991D6 (Deoxycytidine)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/pharmacokinetics
MH  - Cell Line, Tumor
MH  - Deoxycytidine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Magnetite Nanoparticles/*administration & dosage/chemistry
MH  - Mice
MH  - Mice, Nude
MH  - Nanocapsules/*administration & dosage/chemistry
MH  - Nanotechnology
MH  - Pancreatic Neoplasms/*drug therapy/metabolism/pathology
MH  - Urokinase-Type Plasminogen Activator/metabolism
MH  - Xenograft Model Antitumor Assays
MH  - Gemcitabine
PMC - PMC3609912
MID - NIHMS449734
EDAT- 2013/02/14 06:00
MHDA- 2013/09/07 06:00
PMCR- 2014/03/26
CRDT- 2013/02/14 06:00
PHST- 2013/02/14 06:00 [entrez]
PHST- 2013/02/14 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
PHST- 2014/03/26 00:00 [pmc-release]
AID - 10.1021/nn3043463 [doi]
PST - ppublish
SO  - ACS Nano. 2013 Mar 26;7(3):2078-89. doi: 10.1021/nn3043463. Epub 2013 Mar 12.