PMID- 19616049
OWN - NLM
STAT- MEDLINE
DCOM- 20091211
LR  - 20211020
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 139
IP  - 3
DP  - 2009 Nov 3
TI  - Soluble urokinase receptor conjugated to carrier red blood cells binds latent 
      pro-urokinase and alters its functional profile.
PG  - 190-6
LID - 10.1016/j.jconrel.2009.07.003 [doi]
AB  - Coupling plasminogen activators to carrier red blood cells (RBC) prolongs their 
      life-time in the circulation and restricts extravascular side effects, thereby 
      allowing their utility for short-term thromboprophylaxis. Unlike constitutively 
      active plasminogen activators, single chain urokinase plasminogen activator 
      (scuPA) is activated by plasmin proteolysis or binding to its receptor, uPAR. In 
      this study we conjugated recombinant soluble uPAR (suPAR) to rat RBC, forming 
      RBC/suPAR complex. RBC carrying suPAR circulated in rats similarly to naive RBC 
      and markedly prolonged the circulation time of suPAR. RBC/suPAR carrying 
      approximately 3x10(4) suPAR molecules per RBC specifically bound up to 2x10(4) 
      molecules of scuPA, retained approximately 75% of scuPA-binding capacity after 
      circulation in rats and markedly altered the functional profile of bound scuPA. 
      RBC carrying directly conjugated scuPA adhered to endothelial cells, while 
      showing no appreciable fibrinolytic activity. In contrast, RBC/suPAR loaded with 
      scuPA did not exhibit increased adhesion to endothelium, while effectively 
      dissolving fibrin clots. This molecular design, capitalizing on unique biological 
      features of the interaction of scuPA with its receptor, provides a promising 
      modality to deliver a pro-drug for prevention of thrombosis.
FAU - Murciano, Juan-Carlos
AU  - Murciano JC
AD  - Centro Nacional de Investigaciones Cardiovasculares, Madrid Spain.
FAU - Higazi, Abd Al-Roof
AU  - Higazi AA
FAU - Cines, Douglas B
AU  - Cines DB
FAU - Muzykantov, Vladimir R
AU  - Muzykantov VR
LA  - eng
GR  - HL076406/HL/NHLBI NIH HHS/United States
GR  - R01 HL066442/HL/NHLBI NIH HHS/United States
GR  - HD57355/HD/NICHD NIH HHS/United States
GR  - HL66442/HL/NHLBI NIH HHS/United States
GR  - P01 HL076406/HL/NHLBI NIH HHS/United States
GR  - R01 NS053410/NS/NINDS NIH HHS/United States
GR  - HL081864/HL/NHLBI NIH HHS/United States
GR  - R01 HL090697-02/HL/NHLBI NIH HHS/United States
GR  - R21 HL081864/HL/NHLBI NIH HHS/United States
GR  - HL090697/HL/NHLBI NIH HHS/United States
GR  - R01 HL090697/HL/NHLBI NIH HHS/United States
GR  - NS053410/NS/NINDS NIH HHS/United States
GR  - R01 HD057355/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090716
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Drug Carriers)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Prodrugs)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Biotinylation
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - Chemistry, Pharmaceutical
MH  - *Drug Carriers
MH  - Drug Compounding
MH  - Endothelial Cells/drug effects/metabolism
MH  - *Erythrocyte Transfusion
MH  - Erythrocytes/*metabolism
MH  - Fibrinolysis/drug effects
MH  - Fibrinolytic Agents/blood/chemistry/*pharmacology
MH  - Humans
MH  - Prodrugs/chemistry/metabolism/*pharmacology
MH  - Protein Binding
MH  - Rats
MH  - Receptors, Urokinase Plasminogen Activator/*blood/chemistry
MH  - Recombinant Proteins/blood
MH  - *Thrombolytic Therapy
MH  - Urokinase-Type Plasminogen Activator/blood/chemistry/*pharmacology
PMC - PMC2773161
MID - NIHMS137684
EDAT- 2009/07/21 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/11/03
CRDT- 2009/07/21 09:00
PHST- 2009/06/08 00:00 [received]
PHST- 2009/06/29 00:00 [revised]
PHST- 2009/07/08 00:00 [accepted]
PHST- 2009/07/21 09:00 [entrez]
PHST- 2009/07/21 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/11/03 00:00 [pmc-release]
AID - S0168-3659(09)00476-3 [pii]
AID - 10.1016/j.jconrel.2009.07.003 [doi]
PST - ppublish
SO  - J Control Release. 2009 Nov 3;139(3):190-6. doi: 10.1016/j.jconrel.2009.07.003. 
      Epub 2009 Jul 16.