As exogenous ALA (5-aminolevulinic acid) esters can induce the production and accumulation of endogenous photosensitizer PpIX (protoporphyrin IX) in tumor tissues more effectively, they have been the most active photosensitizer prodrug in PDT(photodynamic therapy) field. In this article, along with the procedure of ALA esters based PDT, some primary mechanism and experimental results were considered, which include: first, cellular uptake of ALA esters and its conversion into ALA; second, the production and accumulation of endogenous photosensitizer PpIX induced by eNdogenous ALA esters; last, the photosensitization of PpIX.
Aminolevulinic Acid ; pharmacology ; Esters ; pharmacology ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; Prodrugs ; Protoporphyrins ; pharmacology

The effect of parasitic ions on the results of ultraviolet A (UVA) cross-linking in iontophoresis was still not clear. In this work, the porcine sclera was cross-linked by riboflavin lactate Ringer's solution (group A) and riboflavin normal saline (group B)
Animals ; Collagen ; Cross-Linking Reagents ; Ions ; Iontophoresis ; Permeability ; Photosensitizing Agents/pharmacology* ; Riboflavin ; Sclera ; Swine ; Ultraviolet Rays

Objective: To investigate the effects of low-dose photodynamic therapy on the proliferation, regulation, and secretion functions of human adipose mesenchymal stem cells (ADSCs) and the related mechanism, so as to explore a new method for the repair of chronic wounds. Methods: The experimental research methods were adopted. From February to April 2021, 10 patients (5 males and 5 females, aged 23 to 47 years) who underwent cutaneous surgery in the Department of Dermatology of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) donated postoperative waste adipose tissue. The cells were extracted from the adipose tissue and the phenotype was identified. Three batches of ADSCs were taken, with each batch of cells being divided into normal control group with conventional culture only, photosensitizer alone group with conventional culture after being treated with Hemoporfin, irradiation alone group with conventional culture after being treated with red light irradiation, and photosensitizer+irradiation group with conventional culture after being treated with Hemoporfin and red light irradiation, with sample number of 3 in each group. At culture hour of 24 after the treatment of the first and second batches of cells, the ADSC proliferation level was evaluated by 5-ethynyl-2'-deoxyuridine staining method and the migration percentage of HaCaT cells cocultured with ADSCs was detected by Transwell experiment, respectively. On culture day of 7 after the treatment of the third batch of cells, the extracellular matrix protein expression of ADSCs was detected by immunofluorescence method. The ADSCs were divided into 0 min post-photodynamic therapy group, 15 min post-photodynamic therapy group, 30 min post-photodynamic therapy group, and 60 min post-photodynamic therapy group, with 3 wells in each group. Western blotting was used to detect the protein expressions and calculate the phosphorylated mammalian target of rapamycin complex (p-mTOR)/mammalian target of rapamycin (mTOR), phosphorylated p70 ribosomal protein S6 kinase (p-p70 S6K)/p70 ribosomal protein S6 kinase (p70 S6K) ratio at the corresponding time points after photodynamic therapy. Two batches of ADSCs were taken, and each batch was divided into normal control group, photodynamic therapy alone group, and photodynamic therapy+rapamycin group, with 3 wells in each group. At culture minute of 15 after the treatment, p-mTOR/mTOR and p-p70 S6K/p70 S6K ratios of cells from the first batch were calculated and detected as before. On culture day of 7 after the treatment, extracellular matrix protein expression of cells from the second batch was detected as before. Data were statistically analyzed with one-way analysis of variance and least significant difference test. Results: After 12 d of culture, the cells were verified as ADSCs. At culture hour of 24 after the treatment, the ADSC proliferation level ((4.0±1.0)% and (4.1±0.4)%, respectively) and HaCaT cell migration percentages (1.17±0.14 and 1.13±0.12, respectively) in photosensitizer alone group and irradiation alone group were similar to those of normal control group ((3.7±0.6)% and 1.00±0.16, respectively, P>0.05), and were significantly lower than those of photosensitizer+irradiation group ((34.2±7.0)% and 2.55±0.13, respectively, P<0.01). On culture day of 7 after the treatment, compared with those in normal control group, the expression of collagen Ⅲ in ADSCs of photosensitizer alone group was significantly increased (P<0.05), and the expressions of collagen Ⅰ and collagen Ⅲ in ADSCs of irradiation alone group were significantly increased (P<0.01). Compared with those in photosensitizer alone group and irradiation alone group, the expressions of collagen Ⅰ, collagen Ⅲ, and fibronectin of ADSCs in photosensitizer+irradiation group were significantly increased (P<0.01). Compared with those in 0 min post-photodynamic therapy group, the ratios of p-mTOR/mTOR and p-p70 S6K/p70 S6K of ADSCs in 15 min post-photodynamic therapy group were significantly increased (P<0.01), the ratios of p-p70 S6K/p70 S6K of ADSCs in 30 min post-photodynamic therapy group and 60 min post-photodynamic therapy group were both significantly increased (P<0.01). At culture minute of 15 after the treatment, compared with those in normal control group, the ratios of p-mTOR/mTOR and p-p70 S6K/p70 S6K of ADSCs in photodynamic therapy alone group were significantly increased (P<0.05 or P<0.01). Compared with those in photodynamic therapy alone group, the ratios of p-mTOR/mTOR and p-p70 S6K/p70 S6K of ADSCs in photodynamic therapy+rapamycin group were significantly decreased (P<0.05). On culture day of 7 after the treatment, compared with those in normal control group, the expressions of collagen Ⅰ, collagen Ⅲ, and fibronectin of ADSCs in photodynamic therapy alone group were significantly increased (P<0.01). Compared with those in photodynamic therapy alone group, the expressions of collagen Ⅰ, collagen Ⅲ, and fibronectin of ADSCs in photodynamic therapy+rapamycin group were significantly decreased (P<0.01). Conclusions: Low-dose photodynamic therapy can promote the proliferation of ADSCs, improve the ability of ADSCs to regulate the migration of HaCaT cells, and enhance the secretion of extracellular matrix protein by rapidly activating mTOR signaling pathway.
Adipose Tissue ; Female ; Fibronectins ; Humans ; Male ; Mesenchymal Stem Cells ; Photochemotherapy ; Photosensitizing Agents/pharmacology* ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases

To establish a simple and reliable animal model of skin photo-damage, 20 mice were treated with 8-MOP and exposed to UVA (UVA 320-400 nm) for 24 h. After irradiation, the structure of the epidermis and dermis, collagen fibers, elastic fibers were observed by using HE staining and Weigert technique and compared with the normal controls. The acanthosis and epidermis proliferation with accompanying hyperkeratosis and parakeratosis were observed. Inflammatory infiltration was noted in the dermis. The elastic fibers became coarse, irregularly arranged and clustered, with their number increased. The collagen fibers showed obvious degeneration and some amorphous materials could also be observed. The blood vessels were irregularly dilated and vascular walls were thickened, with infiltration of inflammatory cells. It is concluded that murine photodamage model can be quickly, conveniently and reliably established by means of 8-MOP/UVA.
Dermis/pathology ; Disease Models, Animal ; Epidermis/pathology ; Methoxsalen/*pharmacology ; Photosensitizing Agents/pharmacology ; Skin/*pathology ; Skin Aging ; Ultraviolet Rays

Virus inactivation with photochemistry is being suitable for blood or blood products, methylene blue (MB)/light treatment has been used for viral inactivation of cellular blood components. Twelve new phenothiazines derivatives were designed and synthesized, and were used to test viral inactivation and red cell damage preliminary. Results showed that compound YWW-7 has a satisfactory activity, it could be developed as a new viral inactivation agent for blood products.
Antiviral Agents ; chemical synthesis ; pharmacology ; Methylene Blue ; analogs & derivatives ; chemistry ; Phenothiazines ; chemical synthesis ; pharmacology ; Photosensitizing Agents ; chemical synthesis ; Structure-Activity Relationship ; Virus Inactivation ; drug effects

OBJECTIVETo evaluate the tumor cell-killing effect of photodynamic therapy against human esophageal cancer cells in vitro and identify the main factors affecting the effect.

METHODSHuman esophageal cancer Eca-109 cells were incubated for 24 h in vitro with hematoporphyrin derivative (HpD) and Photofrin at different concentrations prior to exposure to a light energy density of 15 J/cm(2) delivered from a DIOMED 630 PDT system. The cell killing effect was also evaluated for different HpD concentrations combined with 3 light energy densities (10, 30, and 50 J/cm(2)), respectively. The cell survival rate was measured using MTT assay, and fluorescence spectrometry was used to detect the intracellular photosensitizer fluorescence of the tumor cells after incubation with HpD for 4 h.

RESULTSThe cell survival rate after incubation with the two photosensitizers at different concentrations were significantly different, and under the 3 different light energy densities, incubation of the cells with different HpD concentrations also resulted in significantly different cell survival rates (P<0.05). At the 4 low photosensitizer concentrations and with different light energy densities, the cell survival rates were similar (P>0.05), but the 4 higher photosensitizer concentrations resulted in significant difference in the cells survival (P<0.05). Correlation analysis showed that the intracellular photosensitizer concentration was positively correlated to the photosensitizer concentrations in cell incubation (r=0.997).

CONCLUSIONWhen the light source remains constant, the light energy density, the kinds of photosensitizers and their concentrations are the main factors affecting the Eca-109 cell-killing effect of PDT.

Cell Line, Tumor ; Cell Survival ; Dihematoporphyrin Ether ; pharmacology ; Esophageal Neoplasms ; drug therapy ; Hematoporphyrin Derivative ; pharmacology ; Hematoporphyrin Photoradiation ; Humans ; Light ; Photosensitizing Agents ; pharmacology

The killing effect on S180 cells was studied using the combination of protoporphyrin IX and focused ultrasound at the frequency of 2.2 MHz and different intensities. Cell viability was determined by trypan blue exclusion test, morphology changes were evaluated by means of scanning electron microscopy and transmission electron microscopy after ultrasonic exposure. The results indicated that protoporphyrin IX(PPIX) alone showed no significant effect on S180 cells when compared with that of control group. Ultrasound alone and ultrasound combined with PPIX groups showed some anti-tumor effect, which became more noticeable as the ultrasound intensity and PPIX concentration increased, and when the concentration of PPIX increased to 120 microM, the ultrasound combined with PPIX exerted a more significant anti-tumor effect than did the ultrasound alone in the same experiment.
Animals ; Apoptosis ; drug effects ; radiation effects ; Mice ; Mice, Inbred ICR ; Photochemotherapy ; methods ; Photosensitizing Agents ; pharmacology ; Protoporphyrins ; pharmacology ; Sarcoma 180 ; pathology ; therapy ; Sonication ; Tumor Cells, Cultured ; Ultrasonics

This study was purposed to investigate the changes of mitochondrial membrane potential (MMP) and apoptosis-related gene Bcl-2 expression of HL-60 cells treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). HL-60 cell line was used as a model and divided into 4 groups: ALA group, PDT group, ALA+PDT group and control group. The change of MMP was detected by flow cytometry with JC-1 (lipophilic cation 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl-benzimidazol-carbocyanine iodide); the mRNA expression of Bcl-2 was determined by semi-quantitative RT-PCR and real-time PCR. The results demonstrated that MMP significantly decreased after treatment with ALA-PDT and the ratio of cells with disrupted MMP obviously increased in ALA+PDT group in time-dependence manner, as compared with control, ALA and PDT groups (P < 0.05), while no difference between ALA and PDT groups was found. The semi-quantitative RT-PCR and real-time PCR showed that the expression level of Bcl-2 was obviously down regulated at 2 h after ALA-PCT, further down-regulated at 4 h, and lasted in low level at 24 h. It is concluded that ALA-PDT-induced apoptosis of HL-60 cells is associated with its effect on MMP, that is ALA-PDT promotes cell apoptosis through effect on mitochondrial function.
Aminolevulinic Acid ; pharmacology ; Apoptosis ; HL-60 Cells ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; metabolism ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; bcl-2-Associated X Protein ; metabolism

Targeted drug delivery can significantly increase the concentration of the drug in treatment site, and decrease the dosage of drugs, cost of treatment and the drug's adverse effects on the body. So targeted drug delivery is the hotspot of recent studies. This paper reviews the development of targeted drug delivery research in recent years, including three areas: passive targeting, active targeting, and physical and chemical targeting.
Animals ; Antibodies ; metabolism ; Drug Carriers ; Drug Delivery Systems ; methods ; trends ; Emulsions ; Humans ; Liposomes ; Magnetics ; Microspheres ; Nanoparticles ; Pharmaceutical Preparations ; administration & dosage ; Photosensitizing Agents ; pharmacology ; Prodrugs ; Receptors, Cell Surface ; metabolism

The objective of this study was to investigate the effect of ZnPcH(1)-PDT on the lymphoma cells and its mechanism. Human Burkitt's lymphoma cell line CA46 and mouse lymphoma cell line P388 were selected as objects for study. The killing effect of ZnPcH(1)-PDT on cells were assessed by MTT method and colony formation assay; the cell death patterns were analyzed by AO/EB fluorescence stain, TdT-mediated dUTP nick end labeling (TUNEL), DNA ladder assay; and the different proportions of each death pattern were determined by Annexin-V(-FITC)/PI double stains. The results showed that ZnPcH(1)-PDT displayed anti-proliferation effect on both CA46 cells and P388 cells in dose-dependent manner. CA46 cells were less sensitive to PDT than P388 cells (p < 0.05). Furthermore, PDT could induce cell apoptosis in time-dependent manner. The rate of cell apoptosis increased in the PDT-treated cells. The results of Annexin-V(-FITC)/PI stain indicated that early apoptosis was the main death pattern in the PDT-treated CA46 cells, while early apoptosis and necrosis were the main death model in the PDT-treated P388 cells. It is concluded that ZnPcH(1)-PDT can effectively inhibit lymphoma cell proliferation and induce cell apoptosis.
Animals ; Apoptosis ; drug effects ; Burkitt Lymphoma ; pathology ; therapy ; Cell Death ; drug effects ; Cell Line, Tumor ; Humans ; Mice ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; therapeutic use