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Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major. [ABSTRACT FROM AUTHOR]

Melanoma, a severe form of skin cancer intricately linked to genetic and environmental factors, is predicted to reach 100,000 new cases worldwide by 2040, underscoring the need for effective and safe treatment options. In this study, we assessed the efficacy of a photosensitizer called Chlorophyll A (Chl-A) incorporated into hydrogels (HGs) made of chitosan (CS) and poloxamer 407 (P407) for Photodynamic Therapy (PDT) against the murine melanoma cell line B16-F10. The HG was evaluated through various tests, including rheological studies, SEM, and ATR-FTIR, along with cell viability assays. The CS- and P407-based HGs effectively released Chl-A and possessed the necessary properties for topical application. The photodynamic activity of the HG containing Chl-A was evaluated in vitro, demonstrating high therapeutic potential, with an IC50 of 25.99 µM—an appealing result when compared to studies in the literature reporting an IC50 of 173.8 µM for cisplatin, used as a positive control drug. The developed formulation of CS and P407-based HG, serving as a thermosensitive system for topical applications, successfully controlled the release of Chl-A. In vitro cell studies associated with PDT exhibited potential against the melanoma cell line. [ABSTRACT FROM AUTHOR]

This clinical study was developed to primarily evaluate the Complete Cytopathological Response Rate of Cervical Intraepithelial Neoplasms to PDT using chitosan nanocapsules containing Chlorocyan-aluminum phthalocyanine as a photoactive agent. Analyses of the Free Recurrence Interval, toxicity profile (immediate and late), and complications (immediate and late), were secondarily analyzed. This study was previously approved by the National Council of Ethics in Research of Brazil (CONEP), on May 28, 2014, under case number 19182113.4.0000.5009. On the surface of the cervix of each selected patient was applied one mL of the formulated gel, and after 30 min, the light was applied. Reports or the identification of adverse effects and/or complications were observed in follow-up visits, in addition to the collection of cervical oncotic cytology. Out of the total group, 11 (91.7%) primarily treated patients evolved with negative cervical oncotic cytology as soon as in the first evaluation following treatment, and one did not achieve any therapeutic benefit, even after reapplication. Two patients with initially positive response presented cytological recurrence determined by histopathology. A new round of PDT was developed, and both evolved with cytological remission three weeks later, remaining negative until the last follow-up. No important side effects were observed in all the patients. Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy. [ABSTRACT FROM AUTHOR]

The efficacy and safety of photodynamic therapy (PDT) have drawn much attention from clinicians and researchers in the field of anticancer treatments since the last century. Despite the numerous positive outcomes, the works on PDT have brought to light over the last decades, much room remains for improvements in PDT tools, mainly on the photosensitizer molecules. This work reports the first experiments evidencing the photosensitizing activity of DHX-1, a xanthene derivative-based near-infrared probe recently described in the literature, both as a free molecule and associated to a nanostructured lipid carrier. The results show that the DHX-1 presents a broad band of light absorption within the optical window of biological tissues (600–800 nm), generates reactive oxygen species when photoactivated, and is phototoxic against murine breast adenocarcinoma 4T1 cells and murine fibroblast NIH-3T3 in vitro. Moreover, the association of DHX-1 to a nanostructured lipid carrier strongly reduced its phototoxicity against the normal cell line. [ABSTRACT FROM AUTHOR]

• PDT as a potential strategy for the cutaneous leishmaniasis treatment. • Chloroaluminum phthalocyanine liposomes have good stability and can be used in PDT. • Chloroaluminum phthalocyanine liposomes reduces the leishmania load in lesion and spleen. In the Americas, one of the main causative species of cutaneous leishmaniasis is Leishmania (Leishmania) amazonensis. The systemic antimonials remain the most largely used option for disease control. However, this drug has significant toxicity. The development of new alternative therapies, including the identification of effective drugs for topical treatment of cutaneous leishmaniasis, is of utmost interest. In this sense, photodynamic therapy emerges as a new strategy. The aim of this study was to develop the chloroaluminum phthalocyanine-loaded liposome, characterize it, and evaluate its stability and efficacy in the topical treatment of cutaneous leishmaniasis caused by L. (L.) amazonensis. Liposomes composed of egg phosphatidylcholine were prepared by Bangham's method. Storage stability of phthalocyanine-loaded liposomes was evaluated at 30 and 60 days after preparation. For the in vivo evaluation, the animals were infected with L. (L.) amazonensis and divided into groups: chloroaluminium phthalocyanine-loaded liposome, blank liposome, meglumine antimoniate (200 mgSb+5/Kg/day), and control. The lesion size was determined weekly after the beginning of the treatment. Upon completion, parasites were recovered from the skin lesion and spleen and evaluated by limiting dilution assay. Chloroaluminum phthalocyanine-loaded liposomes were stable and showed adequate characteristics for topical administration. The topical chloroaluminum phthalocyanine-loaded liposome was as effective as systemic pentavalent antimony in reducing the parasitic load in the lesion and spleen in infected animals. The present study showed that photodynamic therapy with chloroaluminum phthalocyanine-loaded liposomes is a promising strategy for the treatment of American cutaneous leishmaniasis caused by L. (L.) amazonensis. [ABSTRACT FROM AUTHOR]

• Global statistics have shown a progressive increase in the incidence of skin cancer. • Photodynamic therapy (PDT) has been shown as a promising innovation for the treatment of skin cancers. • Trials selected here evaluated the effectiveness of different PDT protocols for sBCC. • Randomized clinical trials are required to assess long-term effects of complete therapeutic response provided by PDT. Basal cell cancer (BCC) is an epithelial neoplasm that arises from basal cells, which constitute the lower layer of the epidermis. Global statistics have shown the progressive increase in the incidence of skin cancer in several countries. The cumulative exposure to solar radiation (ultraviolet B) in the first two decades of life represents the critical risk for the disease. Preclinical and clinical trials have shown photodynamic therapy (PDT) as a promising innovation for treatment of skin cancers, especially to the non-melanoma group. The authors reviewed trials with photodynamic therapy in superficial basal cell carcinoma with different photosensitizers to better evaluate how PDT modifies the natural history of sBCC. We conclude trials should not assess only the immediate efficacy but the main goal of long-term effectiveness of the protocols in order to generate best evidence for clinical practice. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT), based on the photoactivation of photosensitizers (PSs), has become a well-studied therapy for cancer. Photofrin ® , belonging to the first generation of PS, is still widely used for the treatment of different kinds of cancers; however, it has several drawbacks that significantly limit its general clinical use. Consequently, there has been extensive research on the design of PS molecules with optimized pharmaceutical properties, with aiming of overcoming the disadvantages of traditional PS, such as poor chemical purity, long half-life, excessive accumulation into the skin, and low attenuation coefficients. The rational design of novel PS with desirable properties has attracted considerable research in the pharmaceutical field. This review presents an overview on the classical photosensitizers and the most significant recent advances in the development of PS with regard to their potential application in oncology. [ABSTRACT FROM AUTHOR]

Considering the feasibility of the aluminum phthalocyanine chloride (AlPcCl) application in the topical photodynamic therapy of cutaneous tumors and the lack of HPLC methods capable of supporting skin permeation experiments using this compound, the aim of this study was to obtain a simple and selective chromatographic method for AlPcCl determination in skin matrices. A HPLC-UV/Vis method was developed using a normal-phase column operating at 30°C, an isocratic mobile phase of methanol : phosphoric acid (0.01 M) at 1.5 mL/min, and detection at 670 nm. The method exhibited (i) selectivity against various contaminants found in the different skin layers, (ii) high drug extraction capacity from the hair follicle (>70%) and remaining skin (>80%), and (iii) low limits of detection and of quantification (0.03 and 0.09 μg/mL, resp.). The method was also linear in the range from 0.1 to 5.0 µg/mL (r = 0.9994) and demonstrated robustness with regard to experimental chromatographic parameters according to a factorial design. Lastly, the developed method was successfully tested in in vitro skin permeation studies of AlPcCl, proving its effectiveness in the development of pharmaceutical delivery systems containing this drug for topical photodynamic therapy of skin cancers. [ABSTRACT FROM AUTHOR]

Background: In the photodynamic therapy (PDT), the photosensitizer absorbs light and transfers the energy of the excited state to the oxygen in the cell environment producing reactive oxygen species (ROS), that in its turn, may cause cell damage. In the photothermal therapy (PTT), light also is responsible for activating the photothermal agent, which converts the absorbed energy in heat. Graphene oxide is a carbon-based material that presents photothermal activity. Its physical properties allow the association with the photosensitizer methylene blue and consequently the production of ROS when submitted to light irradiation. Therefore, the association between nanographene oxide and methylene blue could represent a strategy to enhance therapeutic actions. In this work, we report the nanographene oxide-methylene blue platform (NanoGO-MB) used to promote tumor ablation in combination with photodynamic and photothermal therapies against a syngeneic orthotopic murine breast cancer model. Results: In vitro, NanoGO-MB presented 50% of the reactive oxygen species production compared to the free MB after LED light irradiation, and a temperature increase of ∼ 40 °C followed by laser irradiation. On cells, the ROS production by the nanoplatform displayed higher values in tumor than normal cells. In vivo assays demonstrated a synergistic effect obtained by the combined PDT/PTT therapies using NanoGO-MB, which promoted complete tumor ablation in 5/5 animals. Up to 30 days after the last treatment, there was no tumor regrowth compared with only PDT or PTT groups, which displayed tumoral bioluminescence 63-fold higher than the combined treatment group. Histological studies confirmed that the combined therapies were able to prevent tumor regrowth and liver, lung and spleen metastasis. In addition, low systemic toxicity was observed in pathologic examinations of liver, spleen, lungs, and kidneys. Conclusions: The treatment with combined PDT/PTT therapies using NanoGO-MB induced more toxicity on breast carcinoma cells than on normal cells. In vivo, the combined therapies promoted complete tumor ablation and metastasis prevention while only PDT or PTT were unable to stop tumor development. The results show the potential of NanoGO-MB in combination with the phototherapies in the treatment of the breast cancer and metastasis prevention. [ABSTRACT FROM AUTHOR]

• Nanovesicular formulation of OR141 (ORN) could selectively eradicate leukemia cells. • ORN could increase the photosensitizer biodistribution. • In the absence of light, ORN is not toxic for ovarian stromal cells. • Before ovarian autotransplantation, ORN-PDT can potentially be employed as a selective tissue purging strategy to eradicate malignant cells. In 2020, the estimated number of new leukemia cases was higher than 30,000 in girls between 0 and 19 years old. Due to cancer treatment, some of these patients may lose both endocrine and reproductive functions. Transplantation of cryopreserved ovarian tissue is not advised after cancer remission because it has a high risk of reintroducing malignant cells in the patient, potentially leading to leukemia recurrence. To safely transplant the ovarian tissue from these patients and restore their fertility, our goal was to develop a photodynamic therapy (PDT) strategy to eliminate leukemia ex vivo. To this end, we designed, optimized, and characterized OR141-loaded niosomes (ORN) to develop the most effective formulation for ex vivo purging ovarian fragments from chronic myelogenous leukemia cells. After establishing the best ORN formulation, the PDT efficiency of optimized ORN was determined for human ovarian stromal cells and acute myeloid leukemia cell line (HL60). Blank niosomes treatment on ovarian stromal cells causes no significant toxicity, showing that the composition of the nanoparticle is not toxic. On the other hand, the in vitro studies showed that while ovarian stromal cells were still viable (82.04 ± 2.79%) after the treatment by 0.5 µM ORN, the same treatment yielded 95.43 ± 3.89% toxicity and cell death in the cancer cells. In conclusion, our results showed that our novel PDT procedure could be a promising strategy to destroy leukemia cells in ovarian tissue fragments allowing safe transplantation in cancer survivors. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) uses photosensitizing agents, which are delivered in target cells, followed by local application of visible light in specific wavelengths. This reaction produce reactive oxygen species able to induce cell death by apoptosis or necrosis, injured to the local vasculature, and exert important effects on the immune system. Objective The present work evaluated the clinical findings, histomorphological alterations and immunodetection of VEGF after PDT using chloro-aluminum phthalocyanine (AlClPc) entrapped in a lipid nanoemulsion in a split-mouth clinical trial. Material and methods Eight healthy volunteers with clinical indication for extraction were included in the study. Seven days before the extraction 40 ul of nanoemulsion AlClPc 5 μM was injected into gingival tissue followed by irradiation with diode laser, the contralateral side was used as control. Tissue specimens were removed seven days after the PDT and divided into two groups (test and control groups) for histological and immunohistochemical analysis. Patients were monitored at days, 0, 7, 14 and 30 to assess adverse effects of the therapy. Results The therapy was well tolerated by all patients. Adverse effects were short-time and completely reversible. Areas of edema, vascular congestion, and intense vascularization were viewed in gingival samples that received PDT. Additionally, dystrophic calcification was observed in subepithelial region. VEGF showed moderate to strong immunostaining in specimens subjected to PDT. Conclusions Taken together, the results showed that the protocol used in this study mediated by nanoemulsion containing AlClPc is safe for clinical application in gingival tissue and suggests that VEGF is increased after PDT. [ABSTRACT FROM AUTHOR]

Background The increasing incidence of cancer and the search for more effective therapies with minimal collateral effects have prompted studies to find alternative new treatments. Among these, photodynamic therapy (PDT) has been proposed as a very promising new modality in cancer treatment with the lowest rates of side effects, revealing itself to be particularly successful when the photosensitizer is associated with nanoscaled carriers. This study aimed to design and develop a new formulation based on albumin nanospheres containing zincphthalocyanine tetrasulfonate (ZnPcS4-AN) for use in the PDT protocol and to investigate its antitumor activity in Swiss albino mice using the Ehrlich solid tumor as an experimental model for breast cancer. Methods Ehrlich tumor's volume, histopathology and morphometry were used to assess the efficacy of intratumoral injection of ZnPcS4-AN in containing tumor aggressiveness and promoting its regression, while the toxicity of possible treatments was assessed by animal weight, morphological analysis of the liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. In order to evaluate the efficacy of PDT, groups of animals treated with intratumoral injection of doxorubicin (Dox) were also investigated. Results Intratumoral injection of ZnPcS4-AN was found to be efficient in mediating PDT to refrain tumor aggressiveness and to induce its regression. Although tumor volume reduction was not significant, PDT induced a remarkable increase in the necrosis area seen in the tumor's central region, as in other experimental groups, including tumor and Dox treated groups, but also in the tumor's peripheral region. Further, PDT showed minimal adverse effects. Indeed, the use of ZnPcS4-AN in mediating PDT revealed anti-neoplastic activity similar to that obtained while using intratumoral Dox therapy. Conclusions PDT mediated by the new formulation ZnPcS4-AN enhanced the inhibition of tumor growth while producing practically no adverse effects and thus emerges as a very promising nanotechnology-based strategy for solid cancer treatment. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs–CRT, HSP70, HSP90, HMGB1, and IL-1β–were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC50 and a light dose of 25 J/cm2 exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo. [ABSTRACT FROM AUTHOR]

• PDT process highly depends on the light characteristics and photosensitizer's concentration, so they need to be optimized to obtain the most effective protocol. • PDT can be employed as a selective purging strategy to eradicate malignant cells in ovarian tissue fragments before their autotransplantation. • PDT based on AlPc and ZnPc can selectively eradicate the leukemic cells without significant damage to ovarian cells. • In the absence of light, AlPc and ZnPc are not toxic for ovarian stromal cells. Due to the risk of reintroducing malignant cells, autotransplantation of cryopreserved ovarian tissue is not allowed in leukemia patients. In order to restore fertility in these patients, ex vivo purging of ovarian fragments could be proposed as a strategy to eradicate malignant cells before grafting. Photodynamic therapy (PDT), as a clinical-approved modality, is a minimally invasive and selective therapeutic for eliminating malignant cells. The present work aims therefore to evaluate the phototoxicity of two photosensitizers (aluminum phthalocyanine (AlPc) and zinc phthalocyanine (ZnPc)) on leukemia cells. To this end, two lines of malignant cells (K562 and HL-60) and isolated ovarian stromal cells (control) were treated by PDT using a diode laser with various energy densities. Cell viability after the treatment, the amount of generated reactive oxygen species, dark toxicity of the photosensitizers, and single-cell morphology were studied. Our results demonstrated that using irradiation with the energy density of 10 J/cm2, 1 µM AlPc could significantly reduce the viability of K562 (4.73 ± 0.14%) and HL-60 (2.74 ± 0.31%). Similarly, the viability of these cells was reduced (K562 cells: 3.84 ± 0.81%; HL-60 cells: 6.82 ± 3.21%) with 1 µM ZnPc and an energy density of 50 J/cm2. On the other hand, these PDT protocols had no significant effect on stromal cells. These findings indicate that our approach can be a promising strategy for the safe restoration of fertility in leukemia patients. However, further studies are necessary to assess its efficiency in ovarian fragments containing malignant cells to determine their eradication rate and the effect of our treatment on the survival of stromal cells and preantral follicles. [ABSTRACT FROM AUTHOR]

Nanoemulsion, or nanoscaled-size emulsions, is a thermodynamically stable system formed by blending two immiscible liquids, blended with an emulsifying agent to produce a single phase. Nanoemulsion science has advanced rapidly in recent years, and it has opened up new opportunities in a variety of fields, including pharmaceuticals, biotechnology, food, and cosmetics. Nanoemulsion has been recognized as a potential drug delivery technology for various drugs, such as photosensitizing agents (PS). In photodynamic therapy (PDT), PSs produce cytotoxic reactive oxygen species under specific light irradiation, which oxidize the surrounding tissues. Over the past decades, the idea of PS-loaded nanoemulsions has received researchers' attention due to their ability to overcome several limitations of common PSs, such as limited permeability, non-specific phototoxicity, hydrophobicity, low bioavailability, and self-aggregation tendency. This review aims to provide fundamental knowledge of nanoemulsion formulations and the principles of PDT. It also discusses nanoemulsion-based PDT strategies and examines nanoemulsion advantages for PDT, highlighting future possibilities for nanoemulsion use. [Display omitted] • Nanoemulsion increases PSs' bioavailability by minimizing the self-aggregation. • Nanoemulsion can change PSs' solubility and prolong the blood circulation time. • They can increase the PSs' permeability and their physicochemical stability. • Using nanoemulsion, it is possible to combine PDT with other treatments/imaging. [ABSTRACT FROM AUTHOR]

• Aluminum-phthalocyanine delivered by nanoemulsion accumulated into Cryptococcus spp. cells. • Photodynamic therapy led to a photosensitizer concentration-dependent Cryptococcus spp. inhibition. • Sodium butyrate and trichostatin A enhanced the inhibitory effect of photodynamic therapy. Cryptococcosis is a disseminated infection caused mainly by C. neoformans and C. gattii. Limitations for the treatment involve the selection of isolates resistant to conventional antifungal drugs, prolonged treatment time and drugs side effects. This study evaluated the combined effect of histone deacetylase inhibitors (HDACi) and photodynamic therapy (PDT) on the growth of C. neoformans and C. gattii in vitro. Results showed that PDT inhibited yeasts proliferation and enhanced the HDACi-mediated cell viability impairment in Cryptococcus spp. [ABSTRACT FROM AUTHOR]

In this work, we performed the synthesis and characterization of a new class of drug delivery system denominated magnetic nanoemulsion (MNE), which allows the combined action of photodynamic therapy (PDT) and hyperthermia therapy (HPT), designed to work in a synergic way, leading to an expected enhancement of the tumor damage after minimum doses of heat dissipation and/or visible light photosensitization The MNEs were prepared by mixture of two surfactants among the following: Epikuron 170 or Span 80fPoloxamer 188 or Tween 80. The magnetic nanoparticles (MNPs) used in this study are maghemite surface-coated with phosphate (PPT) and the photosensitizer used is Zinc phthalocyanine derivative (ZnPc). [ABSTRACT FROM AUTHOR]

The multidisciplinary field of photodynamic therapy (PDT) is a combination of photochemistry and photophysics sciences, which has shown tremendous potential for cancer therapy application. PDT employs a photosensitizing agent (PS) and light to form cytotoxic reactive oxygen species and subsequently oxidize light-exposed tissue. Despite numerous advantages of PDT and enormous progress in this field, common PSs are still far from ideal treatment because of their poor permeability, non-specific phototoxicity, side effects, hydrophobicity, weak bioavailability, and tendency to self-aggregation. To circumvent these limitations, PS can be encapsulated in liposomes, an advanced drug delivery system that has demonstrated the ability to enhance drug permeability into biological membranes and loading both hydrophobic and lipophilic agents. Moreover, liposomes can also be coated by targeting agents to improve delivery efficiency. The present review aims to summarize the principles of PDT, various PS generations, PS-loaded nanoparticles, liposomes, and their impact on PDT, then discuss recent photodynamic cancer therapy strategies using liposomes as PS-loaded vectors, and highlight future possibilities and perspectives. [Display omitted] [ABSTRACT FROM AUTHOR]

The field of photodynamic therapy (PDT) for treating various malignant neoplasms has been given researchers' attention due to its ability to be a selective and minimally invasive cancer therapy strategy. The possibility of tumor cell infection and hence high recurrence rates in cancer patients tends to restrict autologous transplantation. So, the photodynamic tissue purging process, which consists of selective photoinactivation of the malignant cells in the graft, is defined as a compromising strategy to purify contaminated tissues before transplantation. In this strategy, the direct malignant cells' death results from the reactive oxygen species (ROS) generation through the activation of a photosensitizer (PS) by light exposure in the presence of oxygen. Since new PS generations can effectively penetrate the tissue, PDT could be an ideal ex vivo tissue purging protocol that eradicates cancer cells derived from various malignancies. The challenge is that the applied pharmacologic ex vivo tissue purging should efficiently induce tumor cells with minor influence on normal tissue cells. This review aims to provide an overview of the current status of the most effective PDT strategies and PS development concerning their potential application in ex vivo purging before hematopoietic stem cell or ovarian tissue transplantation. • PDT as a selective and minimally invasive strategy is affordable and widely available. • PDT can be used to inhibit cell infection and destroy cancer cells. • Safe autologous transplantation can be possible using ex vivo PDT-purging. • PDT is an option for ex vivo purging before hematopoietic stem cell transplantation. • Ex vivo PDT has a great potential to be used before ovarian tissue transplantation. [ABSTRACT FROM AUTHOR]

For cancer patients with a high risk of ovarian tissue metastasis, ovarian autotransplantation is not advised due to the potential spread of malignant cells. Ex vivo purging of ovarian fragments may offer a more suitable alternative for fertility restoration. Eradicating malignant cells should be done selectively without affecting follicles or ovarian stromal cells (SCs). As a clinically licensed method, photodynamic therapy (PDT) is a minimally invasive treatment to destroy cancer cells. This study evaluates the effectiveness of nanoemulsions (NE) containing two phthalocyanine photosensitizers; aluminum (III) phthalocyanine (AlPc) and zinc (II) phthalocyanine (ZnPc) in eliminating cancer cells. Human leukemic malignant (HL-60) and ovarian stromal cells (SCs) were treated with AlPc/ZnPc loaded NEs with or without diode laser irradiation. HL-60 leukemia cells in 2D culture were eliminated by treatment with 10 nM AlPc-NE or 0.1 µM ZnPc-NE, while no toxicity was observed in SCs. In 3D culture models, although the cells showed more resistance to the NEs as a result of limited oxygen and photosensitizer penetration, the treatment remained selective for cancer cells. These approaches have the potential to eliminate malignant cells from ovarian tissue fragments. • Nanoemulsions improved the bioavailability and stability of phthalocyanine PSs. • AlPc-NE and ZnPc-NE selectively eradicated cancer cells in 2D and 3D models. • Photodynamic therapy-based purging demonstrated no toxicity in healthy ovarian tissue. • AlPc-NE and ZnPc-NE achieved complete cancer cell elimination after 5 days of treatment. • Nanoemulsion formulations enhanced PS tissue penetration and reduced self-aggregation. [ABSTRACT FROM AUTHOR]

The conventional treatment of onychomycosis, a common fungal infection, consists in the use of local and systemic drugs for 4–6 months. This long protocol is often ineffective due to patient compliance, and usually promotes important collateral effects such as liver and kidney failure. As the alternative, Photodynamic Therapy (PDT) has been used as a noninvasive alternative local treatment for onychomycosis due to the reduction of systemic side effects, fact indicates their use for patients undergoing other systemic treatments. In the present article, we evaluated the effectiveness, as well as the safety of PDT mediated by Aluminium-Phthalocyanine Chloride, entrapped in nanoemulsions, as a drug carrier, to treat onychomycosis in a proof of concept clinical trial. To the date, this is the first published clinical trial that uses PDT mediated by nanomedicines to treat onychomycosis. As main results, we can highlight the safety of the clinical protocol and the antifungal effectiveness similar to the conventional treatments. We observed the (1) clinical cure of 60% of treated lesions; (2) the absence of local and systemic adverse effects; (3) from these clinically healed lesions, 40% were negative for fungal infection in laboratorial exams; and (4) nails that presented negative fungal culture were kept without fungal infection for at least four weeks. The innovation of this approach is the absence of collateral effects, due to the local therapeutically treatment, and the possibility to repeat the treatment without inducing fungal resistance, a fact that indicates this approach as a possible alternative protocol for onychomycosis management. [ABSTRACT FROM AUTHOR]

Background and Objective Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD). Study Design/Material and Methods Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7 days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7 days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA). Results Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone. Conclusions It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive and lethal form of skin cancer, responsible for > 80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we describe the efficacy of the liposomal-AlClPc (aluminum-chloro-phthalocyanine) formulation in PDT study against Ehrlich tumor cells proliferation in immunocompetent swiss mice tongue. Experiments were conduced in sixteen tumor induced mice that were divided in three control groups: (1) tumor without treatment; (2) tumor with 100J/cm2 laser (670nm) irradiation; and (3) tumor with AlClPc peritumoral injection; and a PDT experimental group when tumors received AlClPc injection followed by tumor irradiation. Control groups present similar macroscopically and histological patterns after treatments, while PDT treatment induced 90% of Ehrlich tumor necrosis after 24h of one single application, showing the efficacy of liposome-AlClPc (aluminum-chloro-phthalocyanine) mediated PDT on the treatment of oral cancer. [Copyright &y& Elsevier]

Photodynamic therapy (PDT) is effective in the treatment of different types of cancer, such as basal cell carcinoma and other superficial cancers. However, improvements in photosensitizer delivery are still needed, and the use of PDT against more deeply located tumors has been the subject of many studies. Thus, the goal of this study was to evaluate the efficacy of a nanoemulsion containing aluminium-phthalocyanine (AlPc-NE) as a mediator of photodynamic therapy (PDT-AlPc-NE) against grafted 4T1 breast adenocarcinoma tumors in mice (BALB/c). Short after the appearance of the tumor, the animals were divided into groups (n = 5) as follows: untreated; only AlPc-NE and treated with PDT-AlPc-NE. The tumor volume was measured with a digital calliper at specific times. The presence of metastasis in the lungs was evaluated by microtomography and histopathological analyses. The results show that the application of PDT-AlPc-NE eradicated the transplanted tumors in all the treated animals, while the animals from control groups presented a robust increase in the tumor volume. Still more significantly, microtomography showed the animals submitted the PDT-AlPc-NE to be free of detectable metastasis in the lungs. The histological analysis of the lungs further confirmed the results verified by the microtomography. Therefore, this study suggests that PDT-AlPc-NE is effective in the elimination of experimentally grafted breast tumors in mice and also in preventing the formation of metastasis in the lungs. • Aluminium-phthalocyanine nanoemulsion (AlPc-NE) is readily internalized by murine breast adenocarcinoma 4T1 cells. • The AlPc-NE-mediated photodynamic therapy (PDT) shows nanomolar IC50 against 4T1 cells in vitro. • AlPc-NE-mediated PDT erradicated the primary 4T1 tumors and pulmonar metastases in BALB/c mice. [ABSTRACT FROM AUTHOR]