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Rivista di Chirurgia Cardiaca, Vascolare e Toracica

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The Journal of Cardiovascular Surgery 1998 December;39(6):709-15

lingua: Inglese

Selective tar­get­ing and pho­to­dy­nam­ic destruc­tion of inti­mal hyper­pla­sia by scav­en­ger-recep­tor medi­at­ed pro­tein-chlor­in e6 con­ju­gates

Nagae T., Louie A. Y.*, Aizawa K.°, Ish­i­ma­ru Sh., Wil­son S. E.*

From the Department of Surgery and ° Physiology Tokyo Medical College Hospital, Tokyo, Japan
* Department of Surgery, University of California Irvine Medical Center, Orange, California, USA


Background. Photosensitizers, ­such as Photofrin II or Chloroaluminum-sul­fo­nat­ed phtha­loc­ya­nine accu­mu­late at ­sites of arte­ri­al inju­ry. We ­have exploit­ed ­this prop­er­ty to devel­op a mod­el of pho­to­dy­nam­ic ther­a­py (PDT) for inti­mal hyper­pla­sia. The flu­o­res­cent ­probe [mal­ey­lat­ed-­bovine ser­um albu­min (mal-BSA) con­ju­gat­ed ­with Texas-red] can be selec­tive­ly tar­get­ed to inti­mal mac­ro­phag­es and ­smooth mus­cle ­cells recruit­ed dur­ing for­ma­tion of hyper­pla­sia via a recep­tor-medi­at­ed mech­a­nism.
Methods. In ­this ­study, the pho­to­sen­si­tiz­er chlor­in e6 (Cle6) was con­ju­gat­ed to mal-BSA in a rat mod­el of inti­mal hyper­pla­sia, ­then test­ed the effi­ca­cy of the ­ligand con­ju­ga­tion to pho­to­sen­si­tiz­er (mal-BSA/Cle6) in PDT of inti­mal hyper­pla­sia. Arterial ­wall inju­ry was pro­duced by a bal­loon cath­e­ter ­pulled ­through the abdom­i­nal aor­ta of the rat to ­create a mod­el of inti­mal hyper­pla­sia. Fluorescent com­pounds ­were inject­ed two ­weeks ­after inju­ry.
Results. Four ­hours ­after injec­tion, the inten­sity of flu­o­res­cence ­achieved ­with injec­tion of mal-BSA/Cle6 was high­er for inti­mal hyper­plas­tic ­lesions as com­pared to con­trol are­as. BSA-Cle6 uncon­ju­gat­ed did not dem­on­strate ­such deliv­ery. Two ­weeks ­after bal­loon inju­ry, the ­injured aor­ta was irra­di­at­ed exter­nal­ly ­with an ­argon ­pumped dye ­laser ­four ­hours fol­low­ing the pho­to­sen­si­tiz­er injec­tion. We ­employed two ­total radi­ant expo­sures: 20 J/cm2 and 40 J/cm2. Forty-­eight ­hours ­after PDT, the arter­ies ­were exam­ined his­to­log­i­cal­ly. Intimal hyper­plas­tic ­cells ­were sig­nif­i­cant­ly ­reduced by PDT in the mal-BSA/Cle6 inject­ed ­group (40-100%) ver­sus the Cle6 ­group (0-20%).
Conclusions. Mal-BSA/Cle6 is tak­en up effi­cient­ly by a scav­en­ger path­way, localiz­es in are­as of inti­mal hyper­pla­sia, and func­tions as a pho­to­sen­si­tiz­er for PDT.

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