title: Photophysics and ex vivo biodistribution of β-cyclodextrin-meso-tetra(m-hydroxyphenyl)porphyrin conjugate for biomedical applications.
abstract: Low aqueous solubility of porphyrin-based photosensitizers hampers their clinical use in photodynamic therapy because of complex delivery. In this study, we explore meso-tetra(m-hydroxyphenyl)-21,23H-porphyrin (mTHPP), a potent photosensitizer, covalently attached to β-cyclodextrin (CD-mTHPP) with a focus on topical delivery and cellular uptake. The photophysical properties of CD-mTHPP were examined using steady-state fluorescence and lifetime measurements verifying increased aqueous solubility. Confocal and fluorescence lifetime imaging microscopy on human squamous carcinoma cells (A431) evidenced a cytoplasmic uptake of CD-mTHPP in predominantly monomeric form. CD-mTHPP was also delivered to human skin ex vivo and the skin penetration was assessed using two-photon fluorescence microscopy. The results indicated that CD-mTHPP exhibits improved skin distribution compared to mTHPP alone using aqueous vehicles. Thus the CD-mTHPP conjugate demonstrates improved biodistribution ex vivo compared to mTHPP and is a promising multimodal system for photodynamic therapy.
authors.affiliation: Biomedical Photonics Group, Department of Chemistry and Molecular Biology, University of Gothenburg, Kemivägen 10, SE-412 96, Gothenburg, Sweden. vladimir.kirejev@chem.gu.se marica.ericson@chem.gu.se.
authors.forename: V
authors.initials: V
authors.lastname: Kirejev
authors.forename: A R
authors.initials: AR
authors.lastname: Gonçalves
authors.forename: C
authors.initials: C
authors.lastname: Aggelidou
authors.forename: I
authors.initials: I
authors.lastname: Manet
authors.forename: J
authors.initials: J
authors.lastname: Mårtensson
authors.forename: K
authors.initials: K
authors.lastname: Yannakopoulou
authors.forename: M B
authors.initials: MB
authors.lastname: Ericson
mesh_terms: D001693:Biological Transport, Active; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D036641:Microscopy, Fluorescence, Multiphoton; D055668:Photochemical Processes; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D014867:Water; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D047392:beta-Cyclodextrins; C437342:tetra(3-hydroxyphenyl)porphine; D014867:Water