title: Location of Varying Hydrophobicity Zinc(II) Phthalocyanine-Type Photosensitizers in Methoxy Poly(ethylene oxide) and Poly(l-lactide) Block Copolymer Micelles Using1H NMR and XPS Techniques.
abstract: Hydrophobic zinc(II) phthalocyanine-type derivatives, solubilized in polymeric micelles (PMs), provide a befitting group of so-called nanophotosensitizers, suitable for a variety of photodynamic therapy (PDT) protocols. The factors that influence the success of such products in PDT are the location of the active cargo in the PMs and the nanocarrier-enhanced ability to safely interact with biological systems and fulfill their therapeutic functions. Therefore, the aim of this work was to determine the solubilization loci of three phthalocyanines of varying hydrophobicity, i.e., zinc(II) phthalocyanine (ZnPc), along with its tetrasulfonic acid (ZnPc-sulfo4) and perfluorinated (ZnPcF16) derivatives, loaded in polymeric micelles of methoxy poly(ethylene oxide)-b-poly(l-lactide) (mPEG-b-PLLA), by means of1H nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) combined with ion sputtering. Furthermore, the microenvironment influence upon the chemical and physical status of the solubilized cargo in PMs, expressed by photobleaching and reactive oxygen species (ROS) generation comparing to the same properties of native cargoes in solution, was also evaluated and discussed in regards to the probing location data. The studied phthalocyanine-loaded PMs exhibited good physical stability, high drug-loading efficiency, and a size of less than ca. 150 nm with low polydispersity indices. The formation of polymeric micelles and the solubilization locus were investigated by1H NMR and XPS. ZnPc localized within the PM core, whereas both ZnPcF16and ZnPc-sulfo4- in the corona of PMs. We proved that the cargo locus is crucial for the photochemical properties of the studied phthalocyanines; the increase in photostability and ability to generate ROS in micellar solution compared to free photosensitizer was most significant for the photosensitizer in the PM core. Our results indicate the role of the cargo location in the PM microenvironment and demonstrate that such attempts are fundamental for improving the properties of photosensitizers and their assumed efficiency as nanophotosensitizers in PDT.
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Lamch
authors.affiliation: Department of Advanced Material Technologies, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Tylus
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Jewgiński
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Latajka
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Kazimiera A
authors.identifier: 0000-0002-2020-1761
authors.initials: KA
authors.lastname: Wilk
mesh_terms: D002413:Cations, Divalent; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D055668:Photochemical Processes; D056951:Photoelectron Spectroscopy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D017319:Photosensitizing Agents; D011091:Polyesters; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; C033616:poly(lactide); C028210:monomethoxypolyethylene glycol; D015032:Zinc; C013647:phthalocyanine