phytochlorin and Skin-Neoplasms

Photodynamic therapy (PDT) has been successfully applied in clinical settings to destroy neoplasms, but the efficacy of such a treatment is dependent on the type of neoplasm and the photosynthesizer used. Here, we perform a clinical assessment of PDT for skin metastases of pigmented melanoma using chlorin e(6).. PDT with chlorin e(6) photosensitizer was administered to 14 patients with skin metastases from melanoma (10 females, four males, mean age 49.6 years). Chlorin e(6) at a dose of 5 mg/kg of patient's weight was intravenously injected. The treatment course consisted of two courses of PDT exposure 1 h after intravenous chlorin e(6) injection and 24 h post-injection. The light energy density for each skin tumor was 80-120 J/cm(2) per treatment, with a light power density of 250-300 mW/cm(2).. All skin melanoma metastases that received PDT showed complete regression with no recurrence during the study period. The complete response of all skin metastases from melanoma occurred in eight cases after one PDT treatment. In the remaining six individuals, tumors required multiple PDT courses prior to complete regression. No cases of photodermatitis were registered. The Karnofsky performance scale score of the patients with skin metastases from melanoma showed no significant difference before and after PDT. No patients had significant changes in blood cell counts that would indicate chlorin e(6) systemic toxic effect. Blood chemistry and urinalysis did not show any evidence of chlorin e(6) renal and hepatic injury.. PDT with chlorin e(6) for skin metastases from melanoma is effective and well tolerated. Further clinical investigation of PDT with chlorin e(6) is warranted.

Topics: Chlorophyllides; Female; Humans; Male; Melanoma; Middle Aged; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents; Skin Neoplasms

Although most cutaneous squamous cell carcinoma (cSCC) cases are generally nonlethal and manageable with surgical excision, there ares till significant hazards for patients who are ineligible for surgical resection. We sought to find a suitable and effective treatment for cSCC.. We modified chlorin e6 by adding a hydrogen chain with a six-carbon ring to the benzene ring and named this new photosensitizer as STBF. We first investigated the fluorescence characteristics, cellular uptake of STBF and subcellular localization. Next, cell viability was detected by CCK-8 assay and the TUNEL staining was performed. Akt/mTOR-related proteins were examined by western blot.. STBF-photodynamic therapy (PDT) inhibits cSCC cells viability in a light dose dependent manner. The antitumor mechanism of STBF-PDT might be due to the suppression of the Akt/mTOR signaling pathway. Further animal investigation determined that STBF-PDT led to a marked reduction in tumor growth.. Our results suggest that STBF-PDT exerts significant therapeutic effects in cSCC. Thus, STBF-PDT is expected to be a promising method for the treatment of cSCC and the photosensitizer STBF may be destined for a wider range of applications in photodynamic therapy.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Photochemotherapy; Photosensitizing Agents; Porphyrins; Proto-Oncogene Proteins c-akt; Signal Transduction; Skin Neoplasms; TOR Serine-Threonine Kinases

The study aimed to investigate the chlorin e6 photosensitizer distribution in the tumor and tumor border (5 mm) during low-dose photodynamic treatment and to increase the effectiveness of the therapy for skin neoplasms.. Sensitized boundaries of neoplasms were evaluated by video fluorescence imaging. The study of changes in the chlorin e6 distribution before/after photodynamic therapy and in the process of low-dose photodynamic exposure was carried out by the method of spectral fluorescence diagnostics.. All 19 patients with basal-cell skin cancer had a contrast of chlorin e6 accumulation compared to normal tissues. 3 hours after intravenous administration of the photosensitizer at a dose of 1 mg/kg, the chlorin e6 concentration was: in normal tissues - 0.18 mg/kg, in the tumor - 1.26 mg/kg, in the tumor border - 0.63 mg/kg. In most cases, the fluorescence indices of chlorin e6 in tumor tissues after low-dose photodynamic therapy increased and exceeded the values before light exposure.. Low-dose photodynamic therapy seems to be an optimal method for treating select skin neoplasms, which does not cause severe pain in patients during the light exposure and allows for local increase of the photosensitizer concentration in tumor tissues. This method of photodynamic therapy can improve the effectiveness of thе treatment.

Topics: Chlorophyllides; Humans; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.

Topics: Animals; Cell Line, Tumor; Chlorophyllides; Female; Ligands; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Urea

Chlorin e6 (Ce6) is a promising photosensitizer for tumor photodynamic therapy (PDT). However, the efficacy of Ce6 PDT is limited by Ce6's poor water solubility, rapid blood clearance, and inadequate accumulation in the tumor tissue. This problem is tackled in this work, wherein functionalized superparamagnetic iron oxide nanoparticles (IO-NPs) were used as carriers to deliver Ce6 to melanoma. The IO-NPs were coated with polyglycerol (PG) to afford good aqueous solubility. The chemotherapeutic agent doxorubicin (DOX) was attached to the PG coating via the hydrazone bond to afford affinity to the cell membrane and thereby promote the cell uptake. The hydrophobic nature of DOX also induced the aggregation of IO-NPs to form nanoclusters. Ce6 was then loaded onto the IO nanoclusters through physical adsorption and coordination with surface iron atoms, yielding the final composites IO-PG-DOX-Ce6. In vitro experiments showed that IO-PG-DOX-Ce6 markedly increased Ce6 uptake in mouse melanoma cells, leading to much-enhanced photocytotoxicity characterized by intensified reactive oxygen species production, loss of viability, DNA damage, and stimulation of tumor cell immunogenicity. In vivo experiments corroborated the in vitro findings and demonstrated prolonged blood clearance of IO-PG-DOX-Ce6. Importantly, IO-PG-DOX-Ce6 markedly increased the Ce6 distribution and retention in mouse subcutaneous melanoma grafts and significantly improved the efficacy of Ce6-mediated PDT. No apparent vital organ damage was observed at the same time. In conclusion, the IO-PG-DOX NPs provide a simple and safe delivery platform for efficient tumor enrichment of Ce6, thereby enhancing antimelanoma PDT.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Chlorophyllides; Disease Models, Animal; Doxorubicin; Female; Humans; Magnetic Iron Oxide Nanoparticles; Melanoma; Mice; Nanoparticle Drug Delivery System; Photochemotherapy; Skin Neoplasms; Solubility; Tissue Distribution

The traditional photodynamic therapy (PDT) using a photosensitizer and oxygen under light generates reactive oxygen species (ROS) to kill tumor cells. However, its treatment efficiency is limited by insufficient oxygen in tumor cells. Herein, β-alanine modified gadofullerene nanoparticles (GFNPs) were explored to disrupt tumor vasculatures assisted by light for potent melanoma treatment. As tumor vasculatures are oxygen-rich, the yields of photo-induced singlet oxygen (1O2) by GFNPs are not subjected to the hypoxemia of tumor tissues. Different from the small molecule photosensitizer Chlorin e6 (Ce6), GFNPs realize high-efficiency tumor vascular disruption under light observed by using the mice tumor vascular dorsal skin fold chamber (DSFC) model. The tumor vascular disruption efficiency of GFNPs is size-dependent, and the smallest one (hydration diameter of ca. 126 nm) is more efficient. Mechanistically, the high yields of photo-induced 1O2 by GFNPs can lead to the destruction of the tumor vascular endothelial adherent junction protein-VE cadherin and the decrease of tumor vascular endothelial cells-CD31 proteins, inducing rapid tumor necrosis. In conclusion, our work provides an insight into the design of well-sized nanoparticles to powerfully treat melanoma assisted by light, as well as greatly extending the applications of PDT for robust tumor therapy.

Topics: Animals; beta-Alanine; Cell Death; Chlorophyllides; Female; Fullerenes; Light; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Particle Size; Photochemotherapy; Photosensitizing Agents; Porphyrins; Singlet Oxygen; Skin Neoplasms; Surface Properties

We designed novel polymer-free cubic bicontinuous liquid crystalline dispersions (cubosomes) using monoolein as molecular building block, phospholipids as stabilizers, propylene glycol as hydrotrope. Their kinetic stability was evaluated by analysing the backscattering profiles upon ageing, and the most stable formulation was chosen as potential photosensitizers delivery vehicle for photodynamic therapy (PDT) of human skin melanoma cells. Morphological and topological features of such formulation alternatively loaded with Chlorin e6 or meso-Tetraphenylporphine-Mn(III) chloride photosensitizing dyes were investigated by cryo-TEM, DLS, and SAXS. Bioimaging studies demonstrated that Me45 and MeWo cell lines effectively internalized these cubosomes formulations. Particularly, photodynamic activity experiments proved both the very low cytotoxicity of the cubosomes formulation loaded with Chlorin e6 dye in the "dark" condition, and its significant cytotoxic effect after photoirradiation. The toxic effect recorded when the photosensitizer was encapsulated within the cubosomes was shown to be one order of magnitude higher than that caused by the free photosensitizer. This is the first report of biocompatible polymer-free cubosomes for potential application in both PDT and bioimaging of skin malignant melanoma.

Topics: Cell Line, Tumor; Cell Proliferation; Cell Survival; Chlorophyllides; Drug Carriers; Glycerides; Humans; Kinetics; Liquid Crystals; Manganese; Melanoma; Melanoma, Cutaneous Malignant; Metalloporphyrins; Optical Imaging; Particle Size; Photochemotherapy; Photosensitizing Agents; Porphyrins; Propylene Glycol; Skin Neoplasms; Surface Properties

In this study, we report a gas-forming drug carrier engineered using the liposomal magnetoporation method. The liposomes that were magnetoporated under a magnetic shear stress possessed an opened lipid bilayer hole. A photosensitizing model drug (chlorin e6: Ce6) and 1H-1H-2H-perfluoro-1-hexene (PFH, as a volatile gas-forming agent) were efficiently loaded into the opened holes of the magnetoporated liposomes. PFH in the liposomes is vaporized at 50°C and can initiate liposome destabilization. The experimental results demonstrated that the liposomes were destabilized at 50°C efficiently released Ce6 and enhanced Ce6-mediated phototoxicity against KB tumor cells. As a result, these liposomes induced a significantly increased in vitro and in vivo photodynamic tumor inhibition.

Topics: Animals; Cell Line, Tumor; Chemical Engineering; Chlorophyllides; Female; Fluorocarbons; Humans; Keratinocytes; Light; Liposomes; Magnetic Fields; Magnets; Mice; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Porosity; Porphyrins; Skin Neoplasms; Tumor Burden; Volatilization; Xenograft Model Antitumor Assays

Dermatological photodynamic therapy (DPDT) involves using systematic photosensitizers in combination with light irradiation treatment to eliminate cancer cells. Therefore, a noninvasive fluorescence photodiagnosis system is critical in DPDT for diagnosing target tissues and demarcating the margin of normal tissues. This study proposes a 375-nm ring LED light module in fluorescence imaging for DPDT applications. Image reproducibility (I.R.) and image interference (I.I.) analysis were performed. The results showed that the I.R. value of this fluorescence diagnostic system was higher than 99.0%, and the I.I. from external light sources was lower than 3.0%. In addition, the result of an in vivo study showed that the Chlorin e6 red fluorescence and the scope of distribution of B16-F10 melanoma cells in a mouse ear's vein could be measured clearly using our device; however, the comparison studio with 395-nm LED lights could not focus or capture the red fluorescence effectively.

Topics: Animals; Cell Line, Tumor; Chlorophyllides; Dermoscopy; Equipment Design; Equipment Failure Analysis; Fluorescent Dyes; Lighting; Melanoma; Mice; Mice, Nude; Microscopy, Fluorescence; Photography; Porphyrins; Reproducibility of Results; Sensitivity and Specificity; Skin Neoplasms

Despite wide application of photodynamic therapy (PDT) for the treatment of melanoma skin cancers, there are strong biomedical unmet needs for the effective generation of singlet oxygen after targeted delivery of photosensitizers. Here, we investigated a facile PDT of melanoma skin cancer using transdermal carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. The Cdot-Ce6-HA conjugate was synthesized by the coupling reaction of diaminohexane modified HA (DAH-HA) with the carboxylic group of Ce6. The singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous solution was more significant than that of free Ce6. The enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice were corroborated by confocal microscopy and two-photon microscopy. The laser irradiation after topical treatment with Cdot-Ce6-HA conjugates resulted in complete suppression of melanoma skin cancers. The antitumor effect was confirmed by histological analysis with H&E staining and TUNEL assay for tumor apoptosis. Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of melanoma skin cancers.. To our knowledge, this is the first report on a facile transdermal photodynamic therapy (PDT) of melanoma skin cancer using carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. We found that the singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous solution was more significant than that of free Ce6. Confocal microscopy and two-photon microscopy clearly confirmed the enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice. Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of melanoma skin cancers.

Topics: Administration, Cutaneous; Animals; Apoptosis; Carbon; Cell Line, Tumor; Cell Survival; Chlorophyllides; Diffusion; Melanoma; Mice; Mice, Nude; Nanocapsules; Nanoconjugates; Photochemotherapy; Photosensitizing Agents; Porphyrins; Quantum Dots; Skin Neoplasms

Strategies combining anti-vascular therapy and vascular imaging may facilitate the prediction of early response and outcome in cancer treatment.. The aim of this study was to investigate the relationship between the tumor-associated vasculature in melanoma and to develop an approach for melanoma treatment by utilizing the free form and micelle form of the photosensitizer (PS) chlorin e6 in photodynamic therapy (PDT).. Green fluorescence protein (GFP) expressing B16-F10 melanoma cells were implanted into the mouse ear dermis. Ce6 in free form or in micelle form was administered via the tail vein. An OV100 imaging system was used to record the red fluorescence of Ce6 to obtain real-time vascular images in the GFP tumor.. Compared to free Ce6, Ce6 linked to the micelle-nanocarrier depicted a much clearer vascular image and had an effective vascular destruction by PDT. Micelle Ce6 was localized in lysosomes and in the endoplasmic reticulum of cultured endothelial cells, implying an active endocytosis of the nano-carrier.. Micelle Ce6 can serve as a bifunctional PS for vascular imaging and PDT, which facilitates its delivery in the tumor microenvironment.

Topics: Animals; Cell Line, Tumor; Chemistry, Pharmaceutical; Chlorophyllides; Drug Carriers; Endocytosis; Endoplasmic Reticulum; Genes, Reporter; Green Fluorescent Proteins; Human Umbilical Vein Endothelial Cells; Humans; Lysosomes; Male; Melanoma, Experimental; Mice, Nude; Micelles; Nanoparticles; Neovascularization, Pathologic; Optical Imaging; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms; Time Factors; Tissue Distribution; Transfection; Tumor Microenvironment

Topics: Carcinoma, Basal Cell; Chlorophyllides; Female; Humans; Lasers, Semiconductor; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Povidone; Protoporphyrins; Skin Neoplasms

Tumor response to photodynamic therapy (PDT) is dependent on treatment parameters used. In particular, the light fluence rate may be an important determinant of the treatment outcome. In this clinical case report, we describe the response of angiosarcoma to PDT carried out using different fluence rates and drug and light doses. A patient with recurrent multifocal angiosarcoma of the head and neck was recruited for PDT. A new generation chlorin-based photosensitizer, Fotolon, was administered at a dose of 2.0 to 5.7 mg/kg. The lesions were irradiated with 665 nm laser light for a light dose of 65 to 200 J/cm2 delivered at a fluence rate of 80 or 150 mW/cm2. High dose PDT carried out at a high fluence rate resulted in local control of the disease for up to a year; however, the disease recurred and PDT had to be repeated. PDT of new lesions carried out at a lower fluence rate resulted in tumor eradication. More significantly, it also resulted in spontaneous remission of neighboring and distant untreated lesions. Repeat PDT carried out on a recurrent lesion at a lower fluence rate resulted in eradication of both treated and untreated lesions despite the lower total light dose delivered. Immunohistochemical examination of biopsy samples implies that PDT could have activated a cell-mediated immune response against untreated lesions. Subsequent histopathological examination of the lesion sites showed negative for disease. Our clinical observations show that lower fluence rate PDT results in better outcome and also indicate that the fluence rate, rather than the total light dose, is a more crucial determinant of the treatment outcome. Specifically, lower fluence rate PDT appears to activate the body's immune response against untreated lesions.

Topics: Chlorophyllides; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Immunity, Cellular; Lasers; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Porphyrins; Povidone; Protoporphyrins; Skin Neoplasms