1.
Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones.
Melo, WCMA, Santos, MBD, Marques, BC, Regasini, LO, Giannini, MJSM, Almeida, AMF
Photodiagnosis and photodynamic therapy. 2017;:232-235
Abstract
Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95μgmL-1) incubated by 15min and irradiated with LED 450nm with 24Jcm-2. Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity.
2.
Calcium phosphosilicate nanoparticles for imaging and photodynamic therapy of cancer.
Tacelosky, DM, Creecy, AE, Shanmugavelandy, SS, Smith, JP, Claxton, DF, Adair, JH, Kester, M, Barth, BM
Discovery medicine. 2012;(71):275-85
Abstract
Photodynamic therapy (PDT) has emerged as an alternative modality for cancer treatment. PDT works by initiating damaging oxidation or redox-sensitive pathways to trigger cell death. PDT can also regulate tumor angiogenesis and modulate systemic antitumor immunity. The drawbacks to PDT--photosensitizer toxicity, a lack of selectivity and efficacy of photosensitizers, and a limited penetrance of light through deep tissues--are the same pitfalls associated with diagnostic imaging. Developments in the field of nanotechnology have generated novel platforms for optimizing the advantages while minimizing the disadvantages of PDT. Calcium phosphosilicate nanoparticles (CPSNPs) represent an optimal nano-system for both diagnostic imaging and PDT. In this review, we will discuss how CPSNPs can enhance optical agents and serve as selective, non-toxic, and functionally stable photosensitizers for PDT. We will also examine novel applications of CPSNPs and PDT for the treatment of leukemia to illustrate their potential utility in cancer therapeutics.
3.
Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans.
Thanos, SM, Halliday, GM, Damian, DL
The British journal of dermatology. 2012;(3):631-6
Abstract
BACKGROUND The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. OBJECTIVES To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. METHODS Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. RESULTS High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P < 0·0001); topical and oral nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P < 0·0001). Low irradiance rate PDT was not significantly immunosuppressive in the topical nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045). CONCLUSIONS While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates.
4.
Mechanisms of action of phenanthroperylenequinones in photodynamic therapy (review).
Ali, SM, Olivo, M
International journal of oncology. 2003;(6):1181-91
Abstract
Despite the age-old belief that most anti-cancer agents kill tumor cells by necrosis, recent findings have demonstrated that photosensitizers could also kill tumor cells by triggering genetically programmed series of events termed apoptosis. Cell death by apoptosis is a very neat way to eliminate unwanted cells: no traces are left and the cell contents are never released or accessible to the immune system. Hence there is no inflammation. This is in contrast to death by necrosis. Under these conditions, normally the cell swells and then, when membrane integrity comes under attack, the cell collapses like a balloon and the contents spill out into the extracellular milieu. This may result in an inflammatory response. Because of the relatively clean nature of the apoptotic process, it is desirable to identify compounds that effectively activate the apoptotic pathway. Photodynamic therapy (PDT), a new mode of treatment, is based on the combined use of light-absorbing compounds and light irradiation. Recent developments in understanding the mechanisms of the PDT effect of photosensitizers indicate that a critical factor in the success of the agent is the ability to induce apoptosis in the malignant cell population. Hypericin and Hypocrellins are perylquinones, which are novel natural photosensitizers characterized by high absorption around 470 nm and high singlet oxygen yield. To study the signaling mechanism in vitro we have investigated uptake kinetics, intracellular localization, mode of cell death and mechanisms involved in the photodynamic action following PDT in human cell lines of poorly differentiated (CNE2) and moderately differentiated (TW0-1) nasopharyngeal carcinoma (NPC) and also poorly differentiated colon (CCL-220.1) and bladder (SD) cells.