Photochemotherapy

PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD).

A photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has recently been approved for diagnosis of bladder cancer. The photosensitizers used are in most cases based on the porphyrin structure. These photosensitizers generally accumulate in cancer tissues to a higher extent than in the surrounding tissues and their fluorescing properties may be utilized for cancer detection. The photosensitizers may be chemically synthesized or induced endogenously by an intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) or 5-ALA esters. The therapeutic effect is based on the formation of reactive oxygen species (ROS) upon activation of the photosensitizer by light. Singlet oxygen is assumed to be the most important ROS for the therapeutic outcome. The fluorescing properties of the photosenisitizers can be used to evaluate their intracellular localization and treatment effects. Some photosensitizers localize intracellularly in endocytic vesicles and upon light exposure induce a release of the contents of these vesicles, including externally added macromolecules, into the cytosol. This is the basis for a novel method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins, immunotoxins, gene-encoding plasmids, adenovirus, peptide-nucleic acids and the chemotherapeutic drug bleomycin. The background and present status of PDT, FD and PCI are reviewed.

Masson SAS. Tous droits réservés.-Document téléchargé le 24/11/2021 Il est interdit et illégal de diffuser ce document. 30 L. El Matri et al. Conclusion.-Nos résultats fonctionnels et anatomiques ont montré la supériorité de bevacizumab versus la photothérapie dynamique dans le traitement des NVC du myope fort à long terme.

Refractory neovascular age-related macular degeneration (nAMD) is defined when intravitreal anti-vascular endothelial growth factor injection therapy results in poor response. Treatment of refractory patients determines the success or failure of treatment for nAMD. In this article, we present the definition and mechanism of refractory nAMD, and address various possible therapeutic approaches that can overcome refractoriness, such as switching drugs, increasing injection dosage or frequency, and combination therapy with photodynamic therapy or intravitreal steroid injection.

We report a procedure to prepare highly 14 monodisperse copper telluride nanocubes, nanoplates, and 15 nanorods. The procedure is based on the reaction of a 16 copper salt with trioctylphosphine telluride in the presence 17 of lithium bis(trimethylsilyl)amide and oleylamine. CuTe 18 nanocrystals display a strong near-infrared optical 19 absorption associated with localized surface plasmon 20 resonances. We exploit this plasmon resonance for the 21 design of surface-enhanced Raman scattering sensors for 22 unconventional optical probes. Furthermore, we also 23 report here our preliminary analysis of the use of CuTe 24 nanocrystals as cytotoxic and photothermal agents. 25 C opper-based chalcogenides are used in a wide range of 26

TPE-PDT has advantages over one-photon PDT, including lower collateral damage to healthy tissue and more precise delivery of PDT. As with one-photon PDT, there can be local photochemical depletion of oxygen during TPE-PDT. Here, we investigate model systems and live cells to measure local photosensitizer photobleaching and through it, infer local oxygen consumption in therapeutic volumes of the order 1 pm3. Multilamellar vesicles (MLV) and African green monkey kidney ((3-1) cells were used to study the TPE photobleaching dynamics of the photosensitizer, Verteporfin. It was found that in an oxygen-rich environment, photobleaching kinetics could not be modeled using a mono-exponential function, whereas in hypoxic conditions a mono-exponential decay was adequate to represent photobleaching. A biexponential was found to adequately model the oxygen-rich conditions and it is hypothesized that the fast part of the decay is oxygendependent, whereas the slower rate constant is largely oxygen-independent. Photobleaching recovery studies in the CV-1 cells support this hypothesis.

Nanoparticle-based photonic explorers have been developed for intracellular sensing and photodynamic therapy (PDT). The design employs nanoparticles made of various matrices as multifunctional nanoplatforms, loading active components by encapsulation or covalent attachment. The nanoplatform for biosensing has been successfully applied to intracellular measurements of important ionic and molecular species. The nanoplatform for PDT has shown high therapeutic efficacy in a rat 9L gliosarcoma model. Specifically, a multifunctional nanoplatform that encompasses magnetic resonance imaging (MRI) and PDT agents inside, as well as targeting ligands on the surface, has been developed and applied in vivo, resulting in much improved MRI contrast enhancement and PDT efficacy.

Photodynamic therapy (PDT) is a binary treatment modality that has been used to treat malignant brain tumours for 25 years. The treatment involves the selective uptake of a photosensitizer (PS) by the tumour cells followed by irradiation of the tumour with light of the appropriate wavelength to excite and activate the PS resulting in selective tumour destruction and is a potentially valuable adjunct to surgical excision and other conventional therapies. PDT has undergone extensive laboratory studies and clinical trials with a variety of PS and tumour models. These are discussed with reference mainly to clinical studies involving the PDT of brain tumours.

We are investigating imaging techniques to study the tumor response to photodynamic therapy ͑PDT͒. Positron emission tomography ͑PET͒ can provide physiological and functional information. High-resolution magnetic resonance imaging ͑MRI͒ can provide anatomical and morphological changes. Image registration can combine MRI and PET images for improved tumor monitoring. In this study, we acquired high-resolution MRI and microPET 18 F-fluorodeoxyglucose ͑FDG͒ images from C3H mice with RIF-1 tumors that were treated with Pc 4-based PDT. We developed two registration methods for this application. For registration of the whole mouse body, we used an automatic three-dimensional, normalized mutual information algorithm. For tumor registration, we developed a finite element model ͑FEM͒-based deformable registration scheme. To assess the quality of whole body registration, we performed slice-by-slice review of both image volumes; manually segmented feature organs, such as the left and right kidneys and the bladder, in each slice; and computed the distance between corresponding centroids. Over 40 volume registration experiments were performed with MRI and microPET images. The distance between corresponding centroids of organs was 1.5± 0.4 mm which is about 2 pixels of microPET images. The mean volume overlap ratios for tumors were 94.7% and 86.3% for the deformable and rigid registration methods, respectively. Registration of high-resolution MRI and microPET images combines anatomical and functional information of the tumors and provides a useful tool for evaluating photodynamic therapy.

Purpose: Tookad® is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy. Materials and Methods: Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes. Results: Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained. Conclusions: Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.

Purpose: Vascular targeted photodynamic therapy with WST11 (TOOKADÒ Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. Materials and Methods: An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Results: Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. Conclusions: We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia.

with two sulfonate groups on adjacent phenyl rings; AlPcS 2a , aluminium phthalocyanine with two sulfonate groups on adjacent phenyl rings; E-64, trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane; MTT, 3-[4,5-dimethylthiazol-2-y]-2,5 diphenyltetrazolium bromide a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o c h e m p h a r m

Indocyanine green (ICG) is a near-infrared (NIR) imaging agent and is also an ideal light absorber for laser-mediated photothermal therapy. This NIR dye could serve as a basis of a dualfunctional probe with integrated optical imaging and photothermal therapy capabilities. However, applications of ICG remain limited by its concentration-dependent aggregation, poor aqueous stability, nonspecific binding to proteins and lack of target specificity. To overcome these limitations, a novel ICG-containing nanostructure is designed utilizing the noncovalent self-assembly chemistry between phospholipid-polyethylene glycol (PL-PEG) and ICG. The interactions between both amphiphilic ICG and PL-PEG were studied using absorption and fluorescence spectroscopy. The properties of ICG-PL-PEG nanoprobe, such as absorption and fluorescence spectra, stability, morphology and size distribution, were also investigated. Two representative targeting molecules, namely, a small molecule, folic acid (FA), and a large protein, integrin R v β 3 monoclonal antibody (mAb), were conjugated to the surface of ICG-PL-PEG nanoprobe, displaying the diversity of ligand conjugation. The target specificity was confirmed using three cell lines with different levels of available folate receptors (FRs) or integrin R v β 3 expression via laser scanning confocal microscope and flow cytometry. This targeting ICG-PL-PEG nanoprobe could be internalized into targeted cells via ligand-receptor mediated endocytosis pathway. Our in vitro experiments showed that internalized ICG-PL-PEG could be used for cell imaging and selective photothermal cell destruction. These results represent the first demonstration of the dual functionality of ICG-containing nanostructure for targeted optical imaging and photothermal therapy of cancerous cells. This novel ICG-PL-PEG nanostructure, when conjugated with other therapeutic and imaging agents, could become a multifunctional probe for cancer diagnosis and treatment.

Background In 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), the prodrug ALA is endogenously converted to the active sensitizer protoporphyrin IX (PpIX), while further conversion of PpIX to haem requires iron. Objectives To explore the potential of the iron chelator desferrioxamine (DFO) to enhance PpIX levels and phototoxicity in ALA-PDT. Methods A series of six doses of 2% ALA solution was iontophoresed into the healthy skin of each ventral forearm of 10 volunteers. One arm was pretreated with 20% DFO in aqueous cream, while the control arm received aqueous cream alone, for 16 h. At 5 h following iontophoresis, skinsurface PpIX fluorescence was measured, following which the forearms were simultaneously irradiated with 100 J cm )2 broadband red light. The phototoxic reaction was assessed at 24 h postirradiation as the minimal phototoxic dose (MPD) and with quantification of erythema. Next, eight patients with two superficial basal cell carcinomas or two plaques of Bowen's disease of similar appearance received 20% ALA topically to one lesion and 20% ALA with 20% DFO to the other, for 3 h. Skin-surface PpIX fluorescence was measured at 5 h, following which lesions were irradiated with 100 J cm )2 broadband red light. Results In healthy skin, PpIX fluorescence increased with increasing ALA dose at DFO-treated and untreated sites (P < 0AE0005); PpIX fluorescence peak values were consistently higher in DFOtreated compared with control sites (P < 0AE02). Erythema also correlated with ALA dose (P < 0AE0005), but a significant difference between active and control sites occurred only at low ALA dose (P < 0AE05). The median MPD appeared lower at the DFO-treated sites, at 6 mC vs. 12 mC (P ¼ 0AE06). In contrast, in lesional skin there was no consistent difference in PpIX fluorescence levels between those treated with and without DFO. Conclusions While iron chelation augmented ALA-PDT phototoxicity in normal skin, this occurred only at low ALA dose. Addition of DFO does not appear to confer additional benefit in ALA-PDT of nonmelanoma skin cancers.

We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents. C opper-based chalcogenides are used in a wide range of applications, from thermoelectrics to batteries, including photonics, photovoltaics, and photothermal therapy. 1,2 They are usually p-type semiconductors, due to the presence of copper vacancies. Copper vacancies not only determine charge transport properties but also provide copper chalcogenides with a particularly attractive property: a composition-dependent localized surface plasmon resonance (LSPR) in the nearinfrared (NIR). 3 In particular, copper telluride is characterized by a large thermal power, a direct band gap between 1.1 and 1.5 eV, and superionic conductivity. Copper telluride can exist in a wide range of compositions and phases, which allows tuning its properties by just adjusting the Cu:Te ratio. These properties provide it with both high fundamental interest and technological potential. However, in spite of its relevance, little is known about its properties at the nanoscale, e.g., plasmonics, and a synthetic route to produce uniform copper telluride nanoparticles (NPs) is yet to be reported. While a variety of procedures to prepare sulfide and selenide NPs with excellent uniformity are available, 3,4 one main constraint to produce telluride NPs and particularly copper telluride is the reduced number of tellurium sources available, which narrows the range of accessible reaction conditions to direct telluride NPs nucleation and growth. 65 was mixed with 1 mmol of TOPO and 6 mL of OLA in a 25 66 mL three-neck flask. The mixture was heated under vacuum to 67 100°C to obtain a clear blue solution and kept at this 68 temperature for 30 min to remove low-boiling-point impurities. 69 The temperature was then increased to 160°C, and 0.125 mL 70 of TOP was added. In parallel, a tellurium precursor solution 71 was prepared inside a glovebox by mixing 0.125 mL of a 2 M

To evaluate the effect of photodynamic therapy (PDT) with verteporfin for age-related macular degeneration (AMD) and non-AMD in Thais, and compare with the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) study. The authors prospectively evaluated all data of 51 eyes of 51 patients who had undergone PDT and accomplished a 1-year follow up. The assessments were divided into two categories: group 1 included three subsets of AMD, and group 2 was non-AMD. The first group classified into three subgroups: group 1A: AMD with subfoveal choroidal neovascularization (CNV) and TAP/VIP compatible with recommendation guidelines characteristics, group 1B: AMD with subfoveal CNV and TAP/VIP incompatible, and group 1C: AMD with non-subfoveal CNV. The measurement outcomes comprised of the baseline characteristics, change in visual acuity, and number of treatments. Thirty-eight eyes had CNV-related AMD and 13 eyes were non-AMD...

5-Aminolevulinic acid (ALA) is a natural precursor of protoporphyrin IX (PpIX) and heme in cells. Photodynamic therapy (PDT) utilizes a metabolic imbalance in cancer cells, leading to increased PpIX generation from exogenous ALA. Due to chemical instability of ALA in therapeutic concentrations at pH values larger than 5.0 and at high temperatures, it looses its activity by spontaneous dimerization to 2,5-dicarboxyethyl-3,6-dihydropyrazine (DHPY). ALA esters are now supplementing ALA in PDT, but little is known about their stability.

Medical laser applications based on widespread research and development is a very dynamic and increasingly popular field from an ecological as well as an economic point of view. Conferences and personal communication are necessary to identify specific requests and potential unmet needs in this multi-and interdisciplinary discipline. Precise gathering of all information on innovative, new, or renewed techniques is necessary to design medical devices for introduction into clinical applications and finally to become established for routine treatment or diagnosis. Five examples of successfully addressed clinical requests are described to show the long-term endurance in developing light-based innovative clinical concepts and devices. Starting from laboratory medicine, a noninvasive approach to detect signals related to iron deficiency is shown. Based upon photosensitization, fluorescence-guided resection had been discovered, opening the door for photodynamic approaches for the treatment of brain cancer. Thermal laser application in the nasal cavity obtained clinical acceptance by the introduction of new laser wavelengths in clinical consciousness. Varicose veins can be treated by innovative endoluminal treatment methods, thus reducing side effects and saving time. Techniques and developments are presented with potential for diagnosis and treatment to improve the clinical situation for the benefit of the patient.

Photodynamic therapy (PDT) is a promising option in the treatment of cancer. Efficient photosensitizers are available but many of them have insufficient physico-chemical properties for parenteral application. We have established nanoparticles consisting of human serum albumin (HSA) as a drug carrier system for 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrine (mTHPP) and 5,10,15,20tertrakis(m-hydroxyphenyl)chlorin (mTHPC), two well-known photosensitizers.

Malignancies arising from biliary tract epithelia, or cholangiocarcinoma, are rare tumors that have a poor prognosis. The incidence of these tumors is gradually increasing in many countries. Recent advances have been made in identifying some of the risk factors, and the need for appropriate classification is emerging. The diagnosis of cholangiocarcinoma is often difficult and requires multiple complementary studies. The use of molecular approaches may improve the diagnostic utility of biliary cytology. Treatment of these tumors is complex, and there are many different treatment options. Although surgical resection can be curative, many patients with cholangiocarcinoma are diagnosed at an advanced stage when only palliative approaches can be used. Photodynamic therapy is emerging as a useful modality.

diagnostic and therapeutic procedures. Our recommen- dations were classified as class I, IIA, IIB, or III. For each recommendation we defined the level of supporting evidence as A, B, or C. Results. We identified class I indications for transmyo- cardial revascularization as sole therapy and class IIA indications for transmyocardial revascularization as an adjunct to coronary artery bypass graft surgery

The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs) and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects while using melanoma cells (B16-F10) as model. The liposomal formulations were characterized by both average diameter and zeta potential. The vesicle average size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to 0.230. The zeta potential was significantly positive with values between 48 and 57 mV. The cell viability (CV) after PD and HT treatments was assessed by colorimetric MTT method. Melanoma cells were initially treated with the liposome formulation without light and magnetic field application, revealing cell viability not different from the control cells (p > 0.05). Photodynamic and hyperthermia assays were also applied separately, demonstrating that PD is more effective than HT in reducing the CV of the neoplastic cells. Combined application of both PD and HT treatments was even more effective in reducing the CV of B16-F10 cells. At the highest light dose (2 J/cm 2 ) and under magnetic field activation the CV was about half than PD applied alone. Therefore, the use of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy (PDT) and magnetohyperthermia (MHT) application can be considered as a potential tool to treat malignant melanoma.

In the development of new antibacterial therapeutic approaches to fight multidrug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) represents a well-known alternative to treat local infections caused by different microorganisms. Here we present a polypropylene (PP) fabric finished with citrate-hydroxypropyl-βCD polymer (PP-CD) entrapping the tetra-anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine (TPPS) as photosensitizer eluting scaffold (PP-CD/TPPS) for aPDT. The concept is based on host-guest complexation of porphyrin in the cavities of CDs immobilized on the PP fibers, followed by its sustained and controlled delivery in release medium and simultaneous photo-inactivation of microorganisms. Morphology of fabric was characterized by optical (OM) and scanning electron microscopies (SEM). Optical properties were investigated by UV-vis absorption, steady- and time-resolved fluorescence emission spectroscopy. X-ray Photoelectron Spectroscopy (XPS) and FT-IR ...

Fullerenes are chemical structures made of carbon atoms. The stable form is molecule composed of 60 carbon atoms arranged in a soccer ball-shaped structure. With respect to its electron donor and acceptor capability and photochemical behavior fullerenes can be effective antioxidants and radical scavengers or prooxidants and photosensitizers. These properties of fullerenes have paid attention on their possible biological applications. Results of previous studies point to the great dependance of fullerenes activity upon quality, quantity and geometry of substituents in fullerene derivatives. Some of fullerene derivatives show antiviral and antimicrobial activity, including anti-HIV properties. C60 and its derivatives are able to exhibit cytotoxic and enzyme-inhibiting abilities as well as radical-quenching and antioxidative abilities. Generation of reactive oxygen species under influence of visible light is another ability of fullerene derivetives desired in photodynamic therapy.

Rumiana Bakalova, Hideki Ohba, Zhivko Zhelev, Mitsuru Ishikawa and Yoshinobu Baba are at the Single-Molecule Bioanalysis Laboratory, National Institute for Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu 761-0395, Japan.

Background and objective: The disadvantage of photodynamic therapy (PDT) is in the photosensitizing agents that may stain the tooth structure. There is no register of PDT studies evaluating protocols to minimize that concern. The present study evaluated the efficiency of chemical adjuncts in methylene blue dye (MB) removal after PDT. Materials and methods: Forty single-rooted teeth, after root canal preparation, were filled with 0.01% MB for 5 min, and irradiated with diode laser 660 nm at 40 mW for 240 sec (total energy 9.6 J). The specimens were divided into four groups (n ¼ 10), according to the chemical adjuncts used for dye removal: (a) 2.5% sodium hypochlorite (NaOCl); (b) 2.5% NaOCl þ Endo-PTC cream; (c) 70% ethyl alcohol and (d) saline (control). The crowns were sectioned and fixed in a device. Photographs were taken before the PDT (T0), immediately after (T1) and upon dye removal (T2). The chromatic alterations were evaluated using Adobe Photoshop and K values were determined in four fixed points of each crown. Results: K values (dental staining) increased in all groups when comparing T0 and T1. The effectiveness of the tested adjuncts was, in decreasing order: G1 (À3.11) > G2 (À2.97) > G3 (À1.28) > G4 (À1.19), not observing significant statistical differences (p < 0.05) between G1 and G2 and also between G3 and G4. Conclusions: Protocols to remove photosensitizing dyes should be applied after PDT in order to minimize dental stain. The protocols tested in this study by using 2.5% NaOCl, associated or not with Endo-PTC cream, were effective in avoiding tooth staining caused by MB during PDT.

To evaluate the effect of corneal collagen cross-linking (CXL) on corneal innervation, corneal sensitivity, and tear function in patients with keratoconus. Design: Prospective, interventional case series. Participants: Twenty-four patients with bilateral keratoconus (30 eyes) who presented to the Institute of Vision and Optics, University of Crete, from May 2008 to October 2008. Methods: Patients underwent CXL. Confocal microscopic analysis of corneal sub-basal nerve plexus (total nerve length per image), corneal sensitivity (assessed with the Cochet-Bonnet esthesiometer), basic tear secretion (assessed with Schirmer's I test with anesthesia), and tear film stability (evaluated by means of tear film break-up time [TFBUT]) were assessed preoperatively and at 1, 3, 6, 9, 12, 18, and 24 months postoperatively. Main Outcome Measures: Comparisons between preoperative and each postoperative value of total nerve length per image, corneal sensitivity, Schirmer's I test results, and TFBUT. Results: Total nerve length per image and corneal sensitivity were significantly decreased until postoperative month 6 (for both parameters: PϽ0.05 paired-samples t test at 1, 3, and 6 months postoperatively). Total nerve length per image tended to increase up to 2 years postoperatively, when it reached the preoperative level, but differences with the preoperative values after the sixth post-CXL month were insignificant. The results of Schirmer's I test and TFBUT had no statistically significant difference at any time point. Conclusions: A transient decrease in corneal innervation and corneal sensitivity can be observed up to 6 months after CXL. No significant effect of CXL could be detected on basic tear secretion and tear film stability in our group of patients.

Background  Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply.Objectives  We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs.Methods  ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm−2 violet laser or to 100 mW cm−2 red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA- and MAL-PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency.Results  The pain sensation during ALA-PDT with red light came 22 s sooner than during ALA-PDT with violet light, which is statistically significant (P < 0·05). Moreover, ALA-PDT with red light gave stronger and more persistent erythema than ALA-PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL-PDT with red vs. violet light.Conclusions  Topical ALA-PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA-PDT with red light.

A successful cure of cancer by biopharmaceuticals with intracellular targets is dependent on both specific and sufficient delivery of the drug to the cytosol or nuclei of malignant cells. However, cytosolic delivery and efficacy of membrane-impermeable cancer therapeutics are often hampered by the sequestration and degradation of the drugs in the endolysosomal compartments. Hence, we developed photochemical internalization (PCI) as a site-specific drug delivery technology, which bursts the membrane of endocytic vesicles inducing release of entrapped drugs to the cytosol of light exposed cells. The principle of PCI has been demonstrated in N80 different cell lines and 10 different xenograft models of various cancers in different laboratories demonstrating its broad application potential. PCI-induced endosomal escape of protein-or nucleic acid-based therapeutics and some chemotherapeutics will be presented in this review. With a joint effort by life scientists the PCI technology is currently in a Phase I/II clinical trial with very promising initial results in the treatment of solid tumors.

Porphyrins are the only and most powerful photosensitizers synthesized internally. To understand better the involvement of porphyrins in photosensitization reactions, the heme biosynthetic pathway is first described, as well as the main features of its regulation in both erythroid and hepatic cells. Most disorders of porphyrin metabolism, known as porphyrias, are characterized by porphyrin accumulation. A full discussion of these diseases, their classification and relevant biochemical and clinical signs are presented. Abnormalities in heme biosynthesis in disorders other than porphySias, such as iron-deficient and sideroblastic anemias, lead poisoning, hereditary tyrosinemia, chronic renal disease and alcoholism, are briefly considered. A complete survey of the experimental research on the biosynthesis of porphyrins in tumors and of the important association between cancer and porphyrias is dealt with. The link to photodynamic therapy (PDT) emerges naturally and this is treated from the point of view of using porphyrins endogenously formed by the tumors for their localization and PDT. Finally, considering the nature of the alterations occurring in heme metabolism in tumors, and porphyrias and their ubiquity, a model is discussed where the abnormality of heme synthesis is involved in the initiating lesion of carcinogenesis. The model strongly predicts that the incidence of cancer will be high in cells with abnormal heme metabolism, suggesting that porphyric patients may be at greater risk of the development of cancer. Keywora!~: Porphyrins; Porphyrias; Cancer; Carcinogenesis; Photodynamic therapy loll-1344/93/$24.00 0 1993 -Elsevier Sequoia. All rights reserved A.M. de1 C. Bat& / Po~hyrins, porphytias, cancer and PDT 7 2.3. Regulation

Chlorin and bacteriochlorin derivatives of 5,10,15,20-tetrakis(2chloro-5-sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK-MEL-188 (human melanoma) cell lines upon red light irradiation (cutoff l < 600 nm) at low light doses. Time-dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.

Great progress has been made by Russian and German researchers in recent years (Popp, Voeikov, and others) to examine the biophysical aspects of biophotonic processes in humans. This paper suggests that there is a many-body reality to the way biophysical light interacts with the human self-organization of information that may be achieved by means of biomolecular, metabolic, or neural communication. These systems may merge as mobile energy relay systems similar to what is seen as qi processes in acupuncture science, suggesting a "holomovement" that seeks to confirm itself and increasingly retrieves and uses only the information that serves its exchanges with the environment. This coevolution of evolutionary process levels, expressed in process terms, can be seen as a foundation for a Medicine of Light integrating hidden variables in consciousness studies with functional differentiation and new findings in the biologic sciences. 27 "I regard consciousness as fundamental. I regard matter as a derivative of consciousness."

The aim of this study was to investigate the effectiveness of antimicrobial photodynamic therapy (APDT) using visible light together with water-filtered infrared-A (VIS+wIRA) to eradicate single species of planktonic bacteria and micro-organisms during initial oral bacterial colonization in situ. A broadband VIS+wIRA radiator with a water-filtered spectrum in the range 580-1400 nm was used for irradiation. Toluidine blue (TB) was utilized as a photosensitizer at concentrations of 5, 10, 25 and 50 mg ml "1 . The unweighted (absolute) irradiance was 200 mW cm "2 and it was applied for 1 min. Planktonic cultures of Streptococcus mutans and Enterococcus faecalis were treated with APDT. Salivary bacteria harvested by centrifugation of native human saliva were also tested. In addition, initial bacterial colonization of bovine enamel slabs carried in the mouths of six healthy volunteers was treated in the same way. Up to 2 log 10 of S. mutans and E. faecalis were killed by APDT. Salivary bacteria were eliminated to a higher extent of 3.7-5 log 10 . All TB concentrations tested proved to be highly effective. The killing rate of bacteria in the initial oral bacterial colonization was significant (P50.004) at all tested TB concentrations, despite the interindividual variations found among study participants. This study has shown that APDT in combination with TB and VIS+wIRA is a promising method for killing bacteria during initial oral colonization. Taking the healing effects of wIRA on human tissue into consideration, this technique could be helpful in the treatment of peri-implantitis and periodontitis.

BACKGROUND AND OBJECTIVE. To describe the introduction and use of intense pulsed light (IPL) to treat vascular and pigmented lesions comprising photorejuvenation and its use in photodynamic therapy. METHODS. Review of the medical literature and the authors' experience with IPL. RESULTS AND CONCLUSIONS. IPL is an excellent treatment modality for vascular and pigmented manifestations of photoaging and can be combined with photodynamic therapy for the treatment of early forms of skin cancer.

Light has been employed in the treatment of disease since antiquity. Many ancient civilizations utilized phototherapy, but it was not until early last century that this form of therapy reappeared. Following the scientific discoveries by early pioneers such as Finsen, Raab and Von Tappeiner, the combination of light and drug administration led to the emergence of photochemotherapy as a therapeutic tool. The isolation of porphyrins and the subsequent discovery of their tumor-localizing properties and phototoxic effects on tumor tissue led to the development of modern photodetection (PD) and photodynamic therapy (PDT). This review traces the origins and development of PD and PDT from antiquity to the present day.

Electroporation (EP) is a modern and versatile method that allows the penetration of macromolecules from the intercellular space into cells by forming the channels, under the influence of electromagnetic field. In addition to natural channels and pumps, building cell membranes, resulting electropores an additional way for the transport of macromolecules. The use of this phenomenon has brought good results as a complement to traditional therapeutic methods of treatment during application of cytostatics. EP combination with chemotherapy has reduced the need for surgical intervention (rescue authority). Electroporation is particularly useful for cancer with multidrug resistance, where the dose that enters the interior of cancer cells is limited. Electroporation was also used in transfection of nucleic acids, in photodynamic therapy, cosmetology, as well as the consolidation of the food.

Background Noninvasive procedures for facial rejuvenation are becoming an increasingly popular component of a comprehensive skin care regimen. Concurrently, many new treatment methods are now available to both the plastic surgeon and the aesthetician. Because these techniques have become an integral part of many cosmetic practices, this study aimed to assess the existing evidencebased literature as to their clinical efficacy; to provide an objective overview of some of the most popular noninvasive rejuvenation strategies such as dermaplaning, oxygen therapy, and light therapy; to discuss recent pertinent scientific evidence-based literature; and to provide treatment recommendations based on these findings.

BACKGROUND Laser skin resurfacing was popularized for photoaged and scarred skin 2 decades ago. Since then, several technologic advancements have led to a new generation of delivery systems that produce excellent clinical outcomes with reduced treatment risks and faster recovery times.

Introduction: The aim of this in vitro study was to assess and compare the effect of photoactivated disinfection (PAD) on the bond strength of root canal sealers to human root canal dentin using the push-out test. Methods: Fifteen extracted human mandibular premolar teeth with single and straight roots were used. After the clinical crowns were removed from the cementoenamel junction, root canals were prepared with the ProTaper (Dentsply Maillefer, Ballaigues, Switzerland) rotary system to the size of the F3 file. The smear layer of the roots was removed using 17% EDTA followed by 5.25% sodium hypochlorite (NaOCl) and distillate water. The roots were then randomly divided into 3 groups (n = 5) according to the final irrigation regimen. In group 1, PAD (FotoSan; CMS Dental, Copenhagen, Denmark) was applied to the root canals and light cured for 20 seconds. Group 2 was finally irrigated with a 2% solution of chlorhexidine gluconate, and group 3 served as the control group (NaOCl + EDTA). All the canals were then obturated with the lateral condensation technique using gutta-percha and AH Plus sealer (Dentsply Maillefer) sealer. Onemillimeter-thick horizontal sections from the coronal and midthirds of each root (n: 5 Â 4 = 20) were sliced for the push-out bond strength measurement. The data were converted to megapascals and statistically analyzed using 1-way analysis of variance and the post hoc Tukey test. Results: There was no significant difference among the bond strength of PAD, chlorhexidine gluconate, and NaOCl (P > .05). Conclusions: We conclude that PAD does not adversely affect the bond strength of the AH Plus sealer to root canal dentin and that it can be used for the final disinfection of root canals. (