SDF-1α in glycan nanoparticles exhibits full activity and reduces pulmonary hypertension in rats.
To establish a homing signal in the lung to recruit circulating stem cells for tissue repair, we formulated a nanoparticle, SDF-1α NP, by complexing SDF-1α with dextran sulfate and chitosan. The data show that SDF-1α was barely released from the nanoparticles over an extended period of time in vitro (3% in 7 days at 37 °C); however, incorporated SDF-1α exhibited full chemotactic activity and receptor activation compared to its free form. The nanoparticles were not endocytosed after incubation with Jurkat cells. When aerosolized into the lungs of rats, SDF-1α NP displayed a greater retention time compared to free SDF-1α (64 vs 2% remaining at 16 h). In a rat model of monocrotaline-induced lung injury, SDF-1α NP, but not free form SDF-1α, was found to reduce pulmonary hypertension. These data suggest that the nanoparticle formulation protected SDF-1α from rapid clearance in the lung and sustained its biological function in vivo.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts 02115, United States.
Tao
T
Yin
Andrew R
AR
Bader
Tim K
TK
Hou
Bradley A
BA
Maron
Derrick D
DD
Kao
Ray
R
Qian
Daniel S
DS
Kohane
Diane E
DE
Handy
Joseph
J
Loscalzo
Ying-Yi
YY
Zhang
D000336:Aerosols; D000818:Animals; D054377:Chemokine CXCL12 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D048271:Chitosan / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D019169:Jurkat Cells; D008297:Male; D016686:Monocrotaline; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000336:Aerosols; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D011134:Polysaccharides; D016686:Monocrotaline; D048271:Chitosan; D016264:Dextran Sulfate