Aspirin blocks binding of photosensitizer SnET2 into human serum albumin: implications for photodynamic therapy.
Tin etiopurpurin dichloride (SnET2) is one of the photosensitizers under investigation to be used in photodynamic therapy of prostate cancer. The drug is delivered intravenously, transported in vivo by liposomes and plasma proteins and localized within the prostate. SnET2 exists in two tautomeric forms (I - closed ring, II - open ring) with I converting spontaneously into the more energetically stable form II at physiological pH. Up to approximately 50% of the drug can be carried by serum albumin, although this association can increase photo-bleaching and diminish the drug efficiency. Molecular modeling and force field calculations indicate that Sudlow Site I in human serum albumin (HSA) is the most probable binding site for both forms of SnET2, with the porphyrin moiety nestling between domains IIA and IB, and the esterolytic side group oriented toward domain IIIA of HSA. Other drugs, including aspirin, bind to the same part of HSA. SnET2 does not bind to HSA when pre-incubated with aspirin, which confirms that its place of binding to this protein must be located near Lys199. This observation could be exploited to improve photo-efficiency of SnET2 by finding drugs that could compete with the photosensitizer for binding into Sudlow Site I of HSA.
Skrzypczak-Jankun
E
E
Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH 43614, USA.
Borbulevych
O Y
OY
Melillo
A
A
Keck
R
R
Soriano-Garcia
M
M
Aniola
J
J
Niedre
M
M
Lilge
L
L
Selman
S H
SH
Jankun
J
J
D001241:Aspirin / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
D017319:Photosensitizing Agents; D011166:Porphyrins; D012709:Serum Albumin; C063166:tin etiopurpurin; D001241:Aspirin