Photodynamic Therapy

Animal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo efficacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specificity, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?

A complete set of platinum(II) solketal substituted phthalocyanines has been synthesized and characterized. To evaluate their potential as Type II photosensitizers for photodynamic therapy, comparative studies of their photophysical and photochemical properties with analogous zinc(II) series have been achieved: electronic absorption, fluorescence quantum yields, lifetimes, and fluorescence quenching by benzoquinone, as well as singlet oxygen generation and photodegradation. It appears that platinum(II) phthalocyanines are worth being used as Type II photosensitizers, as they exhibit good singlet oxygen generation and appropriate photodegradation.

We present a study on whether and to what extent subcellular localization may compete favorably with photosensitization efficiency with respect to the overall efficiency of photoinduced cell death. We have compared the efficiency with which two cationic photosensitizers, namely methylene blue (MB) and crystal violet (CV), induce the photoinduced death of human cervical adenocarcinoma (HeLa) cells. Whereas MB is well known to generate singlet oxygen and related triplet excited species with high quantum yields in a variety of biological and chemical environments (i.e., acting as a typical type II photosensitizer), the highly mitochondria-specific CV produces triplet species and singlet oxygen with low yields, acting mostly via the classical type I mechanism (e.g., via free radicals). The findings described here indicate that the presumably more phototoxic type II photosensitizer (MB) does not lead to higher degrees of cell death compared to the type I (CV) photosensitizer. In fact, CV kills cells with the same efficiency as MB, generating at least 10 times fewer photoinduced reactive species. Therefore, subcellular localization is indeed more important than photochemical reactivity in terms of overall cell killing, with mitochondrial localization representing a highly desirable property for the development of more specific/efficient photosensitizers for photodynamic therapy applications.

Harry T. Whelan, MD1a,2,3, John M Houle, BS1a, Noel T. Whelan1a,3, Deborah L. Donohoe, AS, LATG1a, Joan Cwiklinski, MSN, CPNP1a, Meic H. Schmidt, MD1c, Lisa Gould, MD, PhD.1b, David Larson, MD1b, Glenn A. Meyer, MD1a, Vita Cevenini3, Helen ...

Photodynamic therapy(PDT) has been demonstrated to effectively kill human periopathogens in vitro. To evaluate the efficacy of PDT in vivo a series of clinical trials was carried out in multiple centers and populations. Clinical parameters including clinical attachment level, pocket probing depth and bleeding on probing were all evaluated. All groups received the standard of care, scaling and root planing, and the treatment group additionally received a single treatment of PDT. Of the total 309 patients and over 40,000 pockets treated in these 5 trials it was determined that photodynamic therapy provided a statistically significant improvement in clinical parameters over scaling and root planing alone.

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.

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.

The additional optical absorption in tissue resulting from the uptake of exogenous photosensitizers increases the effective attenuation of photoactivating light. This may be significant for the irradiation of solid tumours in photodynamic therapy, since it reduces the depth or volume of tissue treated. The effect has been studied in vitro by using dihaematoporphyrin ether (DHE) and 630 nm light in tissues representing a wide range of absorption and scattering conditions. While the attenuation may be markedly changed by small concentrations of DHE in pure scattering media, tissues with significant inherent light absorption are little affected by the additional absorption of DHE at concentrations relevant to clinical photodynamic therapy. However, it is shown that for other potential photosensitizers such as the phthalocyanines, which have substantially greater absorption at the treatment wavelength than DHE, the penetration of light in tissues may be significantly reduced.

Currently, core-shell heterostructured nanosystems are emerging as next-generation materials due to their potential multifunctionalities in contrast with the more limited single-component counterparts. Systematic investigation of core-shell nanostructures of ZnO and bare-and-doped- Mn2+ ZnS nanocrystals on the surface of magnetite nanoparticles (Fe3O4) was performed. The magnetite cores were prepared via the co-precipitation method and were next treated with an appropriate surfactant. The Fe3O4/(S) (S=ZnO and ZnMnS) core-shell nanoparticles were obtained by an aqueous solution method at room temperature. The structural tests were carried out using an x-ray diffractometer (XRD) which showed the development of crystalline phases of cubic Fe3O4, hexagonal ZnO wurtzite and cubic ZnS. These patterns also established the matching between bare and doped-Mn2+ ZnS diffraction peaks. Broadness of the diffraction peaks evidenced the formation of nanosize phases. The transmission electron microscopy (TEM) confirmed the deposition of a semiconductor shell on the surface of superparamagnetic Fe3O4 nanoparticles. The UV-Vis spectra showed the presence of a strong absorption peak and photoluminescence (PL) spectra displayed the emission peak due to excitonic recombination and a very weak defect-related emission peak suggesting the rearrangement of electronic configuration in the core-shell structures when ZnO is surrounding the core. These spectra also displayed the strong emission peak attributed to paramagnetic ion Mn2+ when acted as dopant in the host ZnS structure. The study of the magnetic properties was carried out using a vibrating sample magnetometer (VSM) which evidenced considerable drop in the saturation magnetization of the Fe3O4/ZnO nanoparticles in comparison to individual Fe3O4 ones. For the Fe3O4/ZnMnS system a slight ferromagnetic behavior at room temperature was observed. The chemical composition of these nanomaterials was performed by x-ray photoelectron spectroscopy (XPS). This elemental analysis demonstrated the presence of Zn on the surface of the magnetic seed at an appropriate shell thickness. These core-shell heterostructured nanoparticles are receiving great potential applications in biomedical areas such as photodynamic therapy.

Photodynamic therapy (PDT) is a therapeutic modality based on the photooxidation of biological materials induced by a photosensitizer, which selectively locates itself in certain tumorous cells or tissues, so that when illuminated by a light of the right length and at a sufficient dose, these cells are destroyed.In dermatology, PDT with topical 5-aminolevulinic acid or 5-methyl aminolevulinate is very effective in the treatment of actinic keratoses, basal cell carcinomas and Bowen&#39;s disease. In addition, very promising results have been obtained in inflammatory pathologies like morphea or sarcoidosis, infections like warts, and cosmetic processes such as photoaging, among others.This article reviews the most significant aspects of PDT in dermatology. First of all, we will review the basic fundamentals of photodynamic treatment. Next, we will outline its clinical applications in dermatology, both in oncological applications and all those dermatological processes in which PDT may ...

One of the major obstacles of successful cancer therapy is cancer drug resistance. The unique tools and applications developed by nanomedicine provide new approaches to surmount this common limitation of current treatment regimens. Nanocarriers that absorb light in the near-infrared spectrum are particularly suitable for this purpose. These nanocarriers can produce heat, release drugs or stimulate the production of physiologically relevant compounds when illuminated with near-infrared light. The current review summarizes the causes contributing to cancer multidrug resistance. The major types of nanocarriers that have been developed in recent years to overcome these hurdles are described. We focus on nanoparticles that are responsive to near-infrared light and suitable to surmount cancer multidrug resistance. Our review concludes with the bottlenecks that currently restrict the use of nanocarriers in the clinic and an outlook on future directions.

The noun phrase "homeopathic medicines" ("homeopathic medicinal products") is clearly counter-logical. It is semantically antithetical in itself. It involves the equivocal counter-logic that confuses and mixes a compound entity-the medicinal product-and a simple entity-the homeopathic simplex-. Its core, medicines, means compound pharmaceutical forms that may contain a number of ingredients, including one, or more than one, active substance. It is totally alien to Homeopathy, which stands on the inherent simplicity in the Principle of similitude, and that in order to cure only applies a simplex-a single dynamized simple active principle-in each treatment phase of every individual case. This fallacious noun phrase is the counter-logical epicenter that instigates not only the long surreptitious confounding task that the homeopathic pharmaindustry carries out in the bosom of homeopathy, but also the current global enantiophatic offensive against "homeopathy supplanted by pseudohomeopathy", for the sake of the social annihilation of perfectly simple, pure Homeopathy. It is, in short, the cornerstone of the global strategy of the pervasive ideological forces of biomedical capitalism to maintain enantiopathy in power, and, under the pretext of the fight against pseudoscience and pseudotherapies, to cover up its pseudo-beneficence and pseudo-scientificity. The counter-logical denomination "homeopathic medicines" is the false premise that scientifically invalidates the content of the homonymous article of the current European Directive and Law of medicinal products for human use. Its legal reality is therefore a serious scientific fraud, and should be repealed.

The use of non-toxic dyes or photosensitizers (PS) in combination with harmless visible light that is known as photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its ...

To investigate the association between cataract surgery and the rate of photodynamic therapy (PDT) for age-related macular degeneration (AMD). Observational population-based retrospective case-control study. All members in a district of the largest health maintenance organization (HMO) in Israel &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 50 years old on January 1, 2001, who did not terminate their membership through May 31, 2005 (139 894 members). All PDT procedures for AMD performed in the study population between January 1, 2001 and May 31, 2005 (283 patients) and all cataract surgeries performed between January 1, 2001 and December 31, 2003 (5913 patients) were documented. We extracted clinical information from the chronic disease registry of the HMO as well as demographic and socioeconomic information. For each patient that underwent cataract surgery, 5 HMO members matched in age, gender, chronic diseases (systemic hypertension, diabetes, hyperlipemia, and ischemic heart disease), place of residence, country of birth and socioeconomic status, who did not undergo cataract surgery, were randomly chosen as controls (n = 29 565). The rate for undergoing PDT at different time periods after cataract surgery. Fifty (0.85%) cataract patients and 94 control cases (0.32%) underwent PDT after cataract surgery (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, chi-square test). A significant rise in PDT rate was noticed in cataract patients compared to controls during the first 6 months after surgery (P = 0.004, chi-square test). Between 6 and 12 months postoperatively, the PDT rates were similar in both groups. However, a more significant rise in PDT rates occurred between 1 and 1.5 years after surgery (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, chi-square test). The Kaplan-Meier PDT-free survival curve of cataract patients was significantly worse than that of the controls (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, chi-square test; P = 33.7, log-rank test). The hazard ratio for cataract patients compared to controls to undergo PDT after surgery was 2.7 (confidence interval = 2.4-5.7). The most significant factors to reduce the time to PDT were advanced age followed by having had cataract surgery, place of birth, socioeconomic status, and hyperlipidemia (Cox proportional hazards survival regression). We identified an increased rate of PDT, presumably for subfoveal AMD, 1 to 1.5 years after cataract surgery.

Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad update on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-ongoing clinical trials.