Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Photodynamic therapy (PDT), because of its good targeting, minimal invasion, and safety, is becoming a very active area in cancer prevention and treatment, in which the photosensitizers have proved to be the core element for PDT. We developed a new HPLC method for analyzing porphyrin photosensitizers using Shiseido Capcell PAK C18 (150 mm x 4.6 mm, 5 µm) as the column at 30 °C, methanol-1% aqueous solution of acetic acid as the mobile phase in a flow rate of 1.0 mL · min(-1) in a gradient elution mode, and the detection wavelength at 380 nm. This method, showing good specificity, precision, accuracy and robusty via methodology validations, can be applied to the purity test and assay of porphyrin photosensitizers, and has played a key guide role in the R&D of the new porphyrin photosensitizer--sinoporphyrin sodium.
Chromatography, High Pressure Liquid ; Photochemotherapy ; Photosensitizing Agents ; chemistry ; Porphyrins ; chemistry

In our screening for photosensitizers from natural resources, four alkaloids were isolated from Glycosmis pentaphylla by various chromatography techniques. Their structures were identified as glycoborinine (1), glybomine B (2), carbalexin A (3) and N-p-coumaroyltyramine (4) by spectral analysis. Their photoactivated antimicrobial activities were evaluated by thin-layer chromatography (TLC) agar overlay assay against Staphylococcus aureus and Bacillus subtilis. It was found that compounds 1 and 4 showed photo-activated antimicrobial activities. Meantime, photo-activated DNA binding activities of these compounds were also assessed by using a specially prepared 1.8 kb DNA fragment and restriction enzymes. Under UVA irradiation, compound 1 showed moderate inhibition on Nde I, Xba I, Nco I and Bcl I which have either 5'-TpA or 5'-ApT and trace or no inhibition on other restriction enzymes. It showed a similar inhibition pattern with the reference 8-methoxypsoralen. However, compounds 2-4 showed no inhibition against any of the restriction enzymes.
Anti-Bacterial Agents ; chemistry ; isolation & purification ; pharmacology ; Bacillus subtilis ; drug effects ; Carbazoles ; chemistry ; isolation & purification ; pharmacology ; Chromatography, Thin Layer ; Coumaric Acids ; chemistry ; isolation & purification ; pharmacology ; DNA Fragmentation ; DNA Restriction Enzymes ; metabolism ; Light ; Molecular Structure ; Photosensitizing Agents ; pharmacology ; Plants, Medicinal ; chemistry ; Protein Binding ; Rutaceae ; chemistry ; Staphylococcus aureus ; drug effects ; Ultraviolet Rays

Our work focuses on the quality control and structural identification of Photocyanine as a cancer therapeutic photosensitizer. Photocyanine is a mixture which contains four ZnPcS2P2 type substituted Phthalocyanine isomers. In order to obtain the single component from Photocyanine, the mixture of four isomers possessing the similar structures and chemical property had been isolated and purified. An HPLC method with a mixture of methanol-acetonitrile-ion-pair buffer as the mobile phase was applied to isolate the four isomers by means of a semi-preparative C18 column. To remove the salts which were mixed in the preparative product, a SPE C18 column was used to separate the salts by elution with water and then the marker component was eluted by methanol. Subsequently, a column of Sephadex LH-20 gel was applied to elute the crudes with methanol to desalination. The purity of the isolated compound was measured by TLC and four different isomers of phthalocyanine were obtained. The chemical structures of them were elucidated by 1H NMR spectra, gCOSY and NOE1D. An HPLC-DAD method was developed for simultaneously determination of four major isomers in Photocyanine with a C18 column (Grace Smart, 150 mm x 4.6 mm ID, 5 microm). The separation was carried out with a gradient program at a flow rate of 1.0 mL x min(-1). The mobile phase was a mixture of acetonitrile and ion-pair buffer (0.01 mol x L(-1) hexadecyl trimethyl ammonium bromide and 0.01 mol x L(-1) potassium dihydrogen phosphate, adjusted the pH value to 6.8 with potassium hydroxide solution). The resolution values of four isomers were 2.5, 1.20, 1.33, and 1.8. Linear regression analysis for four compounds was performed by the external standard method. Four constituents were linear in the concentration range of 0.005 to 10 microg. The values of relative standard deviation (RSD) of intra-day were 0.12%, 0.66%, 0.99%, and 1.21%, respectively. The limits of detection for four compounds were 15 ng, 20 ng, 12 ng, and 25 ng, respectively. This method was simple, accurate and reproducible. The developed method can be successfully applied to analyze isomers in Photocyanine.
Antineoplastic Agents ; analysis ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Indoles ; analysis ; chemistry ; Isomerism ; Molecular Structure ; Organometallic Compounds ; analysis ; chemistry ; Photochemotherapy ; Photosensitizing Agents ; analysis ; chemistry ; Quality Control

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 determine the visible light-induced photodegradation kinetics of two xanthene photosensitizers, phloxine B and uranine, in solution and on the surface of silica TLC plates, and to examine the phototoxicity of residues of degradation, which could provide valuable safety data on the two photosensitizers and other xanthene chemicals when applied in the environment.

METHODSUV-Vis absorption during photodegradation was monitored with a Unico 2102 spectrophotometer. Organic content of samples was measured with a Shimadzu TOC 4100. Phototoxicity tests were carried out using Saccharomyces cerevisiae with the methods modified from Daniels.

RESULTSWhen phloxine B and uranine degraded in solution, their apparent rate constant k was 0.0019 and 0.0027 min(-1), respectively. The total organic carbon (TOC) content decreased by approximately 50% during the 8 h irradiation period, which led to a gradual decrease in phototoxicity of the residues. The photodegradation of photosensitizers on the surface of silica TLC plates was much faster than that in the solution. The apparent rate constant k and the half life of phloxine B were 0.0073 min(-1) and 95 min, respectively.

CONCLUSIONVisible light can rapidly induce photodegradation of phloxine B and uranine. The phototoxicity of residues is also decreased. The environmental risk of applications of phloxine B and uranine is minimal.

Eosine I Bluish ; chemistry ; toxicity ; Fluorescein ; chemistry ; toxicity ; Kinetics ; Molecular Structure ; Photolysis ; Photosensitizing Agents ; toxicity ; Saccharomyces cerevisiae ; drug effects ; radiation effects

Photodynamic therapy (PDT) has been used to treat several types of cancer, and comprises intravascular administration of photosensitizer, uptake by cancer cells, and followed by irradiation of light of appropriate wavelength. Although PDT takes advantage of relative retention of photosensitizer by cancer cells, effective delivery of photosensitizing drugs is of great concern. Several delivery strategies have been employed in PDT. Photosensitizers can be delivered either by passive carriers such as liposomes, micelles, and polymeric particles, or by active targeting using cancer cell-directed ligands or antibodies. Although well-studied colloidal carriers effectively deliver photosensitizer to tumor cells, they are taken up by mononuclear phagocytic system. Delivery system using polymers is an attractive alternative to colloidal carriers, in which hydrophobic drugs are chemically or physically loaded to polymers. Though there are several steps to be solved, targeted delivery system utilizing receptors or antigens abundantly expressed on cancer cell theoretically provides a great deal of advantages over passive system. Selective uptake of photosensitizers by cancer cells may greatly enhance therapeutic efficacy as well as minimizing adverse effects resulting from accumulation in normal tissue. This review discusses various strategies for photosensitizer delivery that have been investigated to date.
Drug Delivery Systems ; Humans ; Liposomes/chemistry ; Micelles ; Neoplasms/*drug therapy ; *Photochemotherapy ; Photosensitizing Agents/*administration & dosage ; Polymers/chemistry/therapeutic use

OBJECTIVETo investigate the killing effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HpD) on human colon carcinoma LoVo and CoLo205 cells in vitro.

METHODSLoVo and CoLo205 cells cultured in vitro were incubated in the presence of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 microg/ml HpD for 4 h and exposed to different light doses delivered using a semiconductor laser at 630 nm with the energy density of 2, 5, 10, and 20 J/cm(2). After further culture for 24 h, the survival rate of LoVo and CoLo205 cells were analyzed by MTT assay, and the cellular fluorescence intensities of HpD were measured with a luminescence spectrometer.

RESULTSHpD-PDT resulted in effective cell killing to a comparable magnitude in LoVo and CoLo205 cells cultured in vitro (P>0.05). The killing effects were positively correlated with the concentration of HpD and the dosage of laser irradiation. Exposure to 20 J/cm(2) resulted in an IC(50) of LoVo and CoLo205 cells of 0.4 and 0.6 microg/ml respectively, which were not significantly different (P>0.05). The cellular HpD fluorescence intensities were also similar between the two cells.

CONCLUSIONHpD-PDT may effectively kill LoVo and CoLo205 cells cultured in vitro.

Animals ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Colonic Neoplasms ; drug therapy ; pathology ; Dose-Response Relationship, Radiation ; Hematoporphyrins ; chemistry ; pharmacology ; Humans ; Lasers ; Photochemotherapy ; methods ; Photosensitizing Agents ; chemistry ; pharmacology ; Spectrometry, Fluorescence