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Jena, Germany

Gaio E.,University of Padua | Scheglmann D.,Biolitec Research GmbH | Reddi E.,University of Padua | Moret F.,University of Padua
Journal of Photochemistry and Photobiology B: Biology | Year: 2016

In cancer photodynamic therapy (PDT), an efficient and homogeneous intratumoral accumulation of the photosensitizer (PS) is required to induce cell damages in the entire tumor mass after light activation. Thus, in this study we investigated penetration ability and photodynamic efficiency of meta-tetra(hydroxyphenyl)chlorin (m-THPC) in standard formulation (Foscan®) and in its non PEGylated and PEGylated liposomal formulations, Foslip® and Fospeg®, in HeLa multicellular spheroids, as in vitro avascular models of solid tumors. Confocal microscopy studies demonstrated that m-THPC fluorescence was confined in the external cell layers of spheroids with a slightly higher accumulation of Foslip® and Fospeg® with respect to Foscan®. Irradiation with red light, following 24 h incubation of spheroids with the m-THPC formulations, caused however photodamages also in cells located in the central part of spheroids, as documented by transmission electron microscopy analyses. Overall, the photodynamic effects of the three m-THPC formulations on HeLa cell spheroids were comparable in terms of cell viability measured with the MTS assay. It is however worth noting that the delivery of m-THPC by liposomes significantly abolished its cytotoxicity in the dark, slightly improved the cellular uptake and, following PDT, promoted cell loss and spheroid disassembling to a higher extent when compared to Foscan®. © 2016 Elsevier B.V. Source


Hamed B.,Free University of Berlin | Haimberger T.V.,Free University of Berlin | Kozich V.,Free University of Berlin | Wiehe A.,Biolitec Research GmbH | Heyne K.,Free University of Berlin
Journal of Photochemistry and Photobiology A: Chemistry | Year: 2014

The two-photon absorption of the photosensitizers 5,10,15,20-tetrakis(m-hydroxyphenyl) porphyrin and the corresponding chlorin has been studied in the near infrared (IR) range using open-aperture z-scan technique. We found cross sections of 10-40 GM in the Q-band region, comparable to values in the Soret-band. Both photosensitizers are promising candidates for IR two-photon photodynamic therapy given the better penetration of IR light into tissue. © 2014 Elsevier B.V. All rights reserved. Source


Moret F.,University of Padua | Scheglmann D.,Biolitec Research GmbH | Reddi E.,University of Padua
Photochemical and Photobiological Sciences | Year: 2013

The folate receptor (FR) is over-expressed in many human tumours and is being intensively studied also in the field of nanomedicine as a target to enhance the selectivity of drug delivery to cancer cells by using nanocarriers bearing folic acid (FA) on their surface. In this study we report the encapsulation of the photosensitizer (PS) meta-tetra(hydroxyphenyl)chlorin (m-THPC) in FA-targeted PEGylated liposomes used as a novel drug delivery system for photodynamic therapy (PDT) of cancer. Our in vitro investigations revealed that only a modest fraction of targeted liposomes were internalized by specific endocytosis in FR-positive KB cells. However, FA-liposomes doubled the uptake of the entrapped m-THPC with respect to un-targeted liposomes and enhanced the photo-induced cytotoxicity in KB cells. In contrast, in FR-negative A549 cells FA-targeted or un-targeted liposomes exhibited a very similar extent of internalization and as a consequence the same photo-killing efficiency. © 2013 The Royal Society of Chemistry and Owner Societies. Source


Haedicke K.,Jena University Hospital | Grafe S.,Biolitec Research GmbH | Lehmann F.,Dyomics GmbH | Hilger I.,Jena University Hospital
Biomaterials | Year: 2013

In our study we wanted to elucidate a time frame for invivo optical imaging of the therapeutic efficacy of photodynamic therapy (PDT) by using a multiplexed imaging approach for detecting apoptosis and vascularization. The internalization of the photosensitizer Foslip® into tongue-squamous epithelium carcinoma cells (CAL-27) was examined invitro and invivo. For detecting apoptosis, annexin V was covalently coupled to the near-infrared dye DY-734 and the spectroscopic properties and binding affinity to apoptotic CAL-27 cells were elucidated. CAL-27 tumor bearing mice were treated with PDT and injected 2 days and 2 weeks thereafter with DY-734-annexin V. PDT-induced changes in tumor vascularization were detected with the contrast agent IRDye® 800CW RGD up to 3 weeks after PDT. A perinuclear enrichment of Foslip® could be seen invitro which was reflected in an accumulation in CAL-27 tumors invivo. The DY-734-annexin V (coupling efficiency 30-50%) revealed a high binding affinity to apoptotic compared to non-apoptotic cells (17.2% vs. 1.2%) with a KD-value of 20nm. After PDT-treatment, the probe showed a significantly higher (p <0.05) contrast in tumors at 2 days compared to 2 weeks after therapy (2-8h post injection). A reduction of the vascularization could be detected after PDT especially in the central tumor areas. To detect the therapeutic efficacy of PDT, a multiplexed imaging approach is necessary. A detection of apoptotic cells is possible just shortly after therapy, whereas at later time points the efficacy can be verified by investigating the vascularization. © 2013 The Authors. Source


Haedicke K.,Friedrich - Schiller University of Jena | Kozlova D.,University of Duisburg - Essen | Grafe S.,Biolitec Research GmbH | Teichgraber U.,Friedrich - Schiller University of Jena | And 2 more authors.
Acta Biomaterialia | Year: 2015

Photodynamic therapy (PDT) of tumors causes skin photosensitivity as a result of unspecific accumulation behavior of the photosensitizers. PDT of tumors was improved by calcium phosphate nanoparticles conjugated with (i) Temoporfin as a photosensitizer, (ii) the RGDfK peptide for favored tumor targeting and (iii) the fluorescent dye molecule DY682-NHS for enabling near-infrared fluorescence (NIRF) optical imaging in vivo. The nanoparticles were characterized with regard to size, spectroscopic properties and uptake into CAL-27 cells. The nanoparticles had a hydrodynamic diameter of approximately 200 nm and a zeta potential of around +22 mV. Their biodistribution at 24 h after injection was investigated via NIRF optical imaging. After treating tumor-bearing CAL-27 mice with nanoparticle-PDT, the therapeutic efficacy was assessed by a fluorescent DY-734-annexin V probe at 2 days and 2 weeks after treatment to detect apoptosis. Additionally, the contrast agent IRDye® 800CW RGD was used to assess tumor vascularization (up to 4 weeks after PDT). After nanoparticle-PDT in mice, apoptosis in the tumor was detected after 2 days. Decreases in tumor vascularization and tumor volume were detected in the next few days. Calcium phosphate nanoparticles can be used as multifunctional tools for NIRF optical imaging, PDT and tumor targeting as they exhibited a high therapeutic efficacy, being capable of inducing apoptosis and destroying tumor vascularization. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source

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