Retrograde delivery of photosensitizer (TPPp-O-beta-GluOH)3 selectively potentiates its photodynamic activity

Bioconjugate Chemistry
Mohamed AmessouLudger Johannes

Abstract

Photodynamic therapy involves administration of a photosensitizing drug and its subsequent activation by visible light of the appropriate wavelength. Several approaches to increasing the specificity of photosensitizers for cancerous tissues and, in particular, through their conjugation to ligands that are directed against tumor-associated antigens have been investigated. Here, we have studied the delivery of the photocytotoxic porphyrin compound TPP(p-O-beta-D-GluOH)3 into tumor cells that overexpress the glycosphingolipid Gb3, using the Gb3-binding nontoxic B-subunit of Shiga toxin (STxB) as a vector. To allow for site-directed chemical coupling, an STxB variant carrying a free sulfhydryl moiety at its C-terminal end has been used. Binding affinity, cellular uptake, singlet oxygen quantum yield, and phototoxicity of the conjugate have been examined. Despite some effect of coupling on both the photophysical properties of TPP(p-O-beta-D-GluOH)3 and the affinity of STxB for its receptor, the conjugate exhibited a higher photocytotoxic activity than the photosensitizer alone and was exquisitely selective for Gb3-expressing tumor cells. Furthermore, our data strongly suggest that STxB-mediated retrograde delivery of the photosensit...Continue Reading

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Citations

Mar 16, 2012·The Journal of Biological Chemistry·Mitsumasa SaitoClifford Lingwood
Jan 28, 2014·Progress in Lipid Research·Kirsten SandvigTore Skotland
Nov 4, 2008·Expert Opinion on Drug Delivery·Stéphane A SibaniRyan F Donnelly
Apr 27, 2017·Macromolecular Bioscience·Claudia Battistella, Harm-Anton Klok
Dec 22, 2009·Nature Reviews. Microbiology·Ludger Johannes, Winfried Römer
Dec 22, 2015·Applied Microbiology and Biotechnology·Yau Sang Chan, Tzi Bun Ng
Jan 25, 2011·Microbial Biotechnology·Nikolai EngedalKirsten Sandvig
Nov 12, 2014·Biochemistry. Biokhimii︠a︡·A A RosenkranzA S Sobolev
Mar 21, 2018·Molecular and Cellular Biology·Juan F ArandaCarlos Fernández-Hernando
Jun 3, 2021·Toxins·Clifford Lingwood

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