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Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar 2 TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at ∼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I 3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC 50 value of 0.45 μM, and phototherapeutic index of 25.8. Flow cytometry revealed that I 3 could induce distinct cell apoptosis. In vivo studies revealed that compound I 3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I 3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In quest for new photosensitizers (PSs) with remarkable antitumor photodynamic efficacy, a series of fifteen quaternary ammonium (QA) cations conjugated 5,15-diaryltetranaphtho[2,3]porphyrins (Ar 2 TNPs) was synthesized and evaluated in vitro and in vivo to understand how variations in the length of the alkoxy group and the kind of QA cations on meso-phenyl influence the photodynamic antitumor activity. All final compounds (I 1-5 , II 1-5, and III 1-5 ) exhibited robust absorption at 729 nm with significant bathochromic shift and high molar extinction coefficients (1.16 × 10 5 -1.41 × 10 5  M -1  cm -1 ), as well as other absorptions at 445, 475, 651, and 714 nm for tumors and other diseases of diverse sizes and depths. Upon exposure to 474 nm light, they displayed intense fluorescence emission with fluorescence quantum yields ranging from 0.32 to 0.43. The ability to generate reactive oxygen species (ROS) was also quantified, attaining a maximum rate of up to 0.0961 s -1 . The IC 50 values of all the compounds regarding phototoxicity and dark toxicity were determined using KYSE-150 cells, and the phototoxicity indices were calculated. Among these compounds, III 1 demonstrated the highest phototoxic index with minimal dark toxicity, and suppressed successfully the growth of esophageal carcinoma xenograft with favorable tolerance in vivo. Furthermore, the histological results showed III 1 -mediated PDT had a significant cytotoxic effect on the tumor. These outcomes underscore the potential of III 1 as a highly effective antitumor photosensitizer drug in photodynamic therapy (PDT)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

To discover new photosensitizers with long wavelength UV-visible absorption, high efficiency, and low side effects for photodynamic therapy, here, a series of novel thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. These compounds had a distinct absorption band at 640-680 nm, fluorescence emission at 650-760 nm, and good solubility with anti-aggregation effects. These new compounds possessed obvious singlet oxygen generation ability and photodynamic anti-Eca-109 cancer cells activities in vitro. Among them, compound II 4 could be well uptaked by Eca-109 cells, and result in the apoptosis after laser irradiation, and have outstanding photodynamic efficiency both in vitro and in vivo. Therefore, II 4 could be considered as a potential photosensitizer drug candidate for PDT and photo-imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the pursuit of new potent photosensitizers (PSs) for photodynamic therapy (PDT) with better efficacy, a series of 5,15-diaryltetranaphtho [2,3]porphyrins (Ar 2 TNPs) with two or four carboxyalkoxy groups were designed, synthesized, and evaluated. These new compounds exhibited strong, broad and red-shifted UV-vis absorptions at 729 nm and other strong absorptions at 446, 475, 650, 659, 714 nm for tumors and other diseases of varying sizes and depths. They possess high molar extinction coefficients (0.95 × 10 5 -1.48 × 10 5  M -1  cm -1 ), good singlet oxygen quantum yields and photodynamic antitumor effects towards Eca-109 cells in vitro. It is suggested that the extension of porphyrin with naphthalene into Ar 2 TNP results into remarkable improvement of photophysical characteristics, while the introduction of carboxyalkoxy groups on meso-phenyl can significantly improve the solubility and photodynamic effects in vitro and in vivo. Notably, compound II 3 can localize primarily in lysosomes of Eca-109 cells and induce substantial cell apoptosis after PDT. It can also selectively accumulate in tumor tissues and be traced real-timely through in vivo fluorescence imaging with distinctive inhibition of tumor growth. Therefore, compound II 3 deserves to be considered as a promising PDT drug candidate for individualized tumor real-time tracing and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The discovery of new photosensitizer drugs with long wavelength Uv-vis absorption, high efficiency and low side-effects is still a challenge in photodynamic therapy. Here a series of novel meso-substitutedphenyl thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. All these compounds have strong absorption at 640-680 nm and obvious fluorescence emission at 650-760 nm. They exhibited high singlet oxygen generation ability and significant photodynamic efficiency against Eca-109 cancer cells. Compounds II 4 , II 6 , II 9 , II 10 and II 13 could generate intracellular ROS and induce cell apoptosis after laser irradiation, which displayed superior photodynamic efficiency against Eca-109 cells than Temoporfin in vitro and in vivo. Among them, compound II 4 specifically exhibited excellent anti-tumor efficacy, and could be selected as a new drug candidate for PDT., Competing Interests: Declaration of competing interest All authors have read, approved and agreed to the submission of the manuscript, and have declared no conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Aim: A study of the enhancement of photodynamic activities of pyropheophorbide-a using PG-Ag-PPa nanoconjugates. Materials & methods: The nanoconjugates were formulated from silver nanoparticles and PPa via amide linkage, then characterized, and their photodynamic activities were examined. Results: The nanoconjugates displayed a higher rate of reactive oxygen species generation, commendable cellular uptake by Eca-109 cancer cells, higher photocytotoxicity toward the cancer cells and better bio-safety. They revealed strong antibacterial activity against Escherichia coli following internal reactive oxygen species generation and membrane disintegration. The in vivo anticancer studies confirmed higher cytotoxicity of the nanoconjugates toward cancer cells and better safety than PPa. Conclusion : Therefore, PG-Ag-PPa nanoconjugates could be considered potential nano photosensitizers for photodynamic therapy of tumors and bacterial infection with good bio-safety.

Background: Photodynamic therapy (PDT) of cancer has been limited by the poor solubility of most photosensitizers, use of high drug dosages, and the pH difference between the tumor tissue microenvironment (slightly acidic) and the bloodstream. These affect cellular uptake, selectivity and singlet oxygen generation. Materials & methods: We formulated Photinia glabra -green synthesized zinc oxide-protoporphyrin IX (PG-ZnO-PP) nanoconjugates by conjugating the ZnO nanoparticles enriched with amino groups and PP. Results: PG-ZnO-PP nanoconjugates showed higher rate of reactive oxygen species generation, improved cellular uptake in the acidic pH and lower IC 50 toward Eca-109 cells for PDT. Conclusion: PG-ZnO-PP nanoconjugates are a potential solution to reducing drug dosage of PP through improved drug uptake, for enhanced targetability and reduced skin photosensitivity with improved PDT efficacy.

The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I 1-6 ) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660 nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I 2 ) and stronger phototoxicity (except I 4 ) against Eca-109 tumor cells than HMME. Among them, I 3 possessed the highest singlet oxygen quantum yield (Φ Δ  = 0.205), the lower dark toxicity and the strongest phototoxicity (IC 50  = 3.5 μM) in vitro. The findings indicated the compounds I 3 had the potential to become anti-tumor agents for PDT., (© 2022. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Purpose: Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy., Methods: The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I 1-6 , II 1-4 ) were tested. The cytotoxicity of I 1-6 and II 1-4 were measured by MTT assay. The pathway of cell death was studied by flow cytometry. In vivo photodynamic efficacy of I 3 and II 2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined., Results: 5,15-Diaryl-10,20-dihalogeno porphyrins I 1-6 and II 1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λ max  = 660 nm) displayed a red shift around 30 nm compared to the unhalogenated porphyrins PS 1 (λ max  = 630 nm). The singlet oxygen generation rates of I 1-6 and II 1-4 were significantly higher than PS 1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II 4 exhibited appropriate absorption in the phototherapeutic window, higher 1 O 2 generation rate (k = 0.0061 s -1 ), the strongest phototoxicity (IC 50  = 0.4 μM), lower dark toxicity, high generation of intracellular ROS in Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II 4 mediated PDT., Conclusion: All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II 4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). We study the photodynamic action against A549 human lung cancer cells using PS based on polycationic derivatives of synthetic bacteriochlorin., Methods: The efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against A549 lung cancer cells were studied in vitro using immunocytochemical and morphological methods., Results: It was found that PS based on tetracationic and octacationic derivatives of synthetic bacteriochlorin induce necrosis, apoptosis, decreasing of proliferative and mitotic activity, as well as reducing the number of ALDH1-positive cancer cells with signs of stem cells in A549 human lung cancer cell culture. The IC 50 values (concentration of a PS that reduces cells survival by 50%) were about 0.69 μM for tetracationic PS and 0.57 μM for octacationic PS under irradiation at 30 J/cm 2 while in the "dark" control they were higher than 100 μM for both PSs., Conclusions: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high phototoxicity against A549 cancer cells caused by the induction of necrosis and apoptosis of cancer cells, including cells with signs of stemness, and a sharp decrease of mitotic and proliferative activity., (Copyright © 2022. Published by Elsevier B.V.)

The synthesis, photophysicochemical and photodynamic therapy (PDT) activities of benzothiazole substituted zinc phthalocyanine (Pc): 1 (asymmetrically substituted and composed of no charges), 2 (asymmetrically substituted and composed of three positive charges), and 3 (symmetrically substituted and composed of four positive charges), are presented. The triplet and singlet oxygen quantum yields were highest for complex 2 showing the importance of asymmetry and charge. The complexes are covalently and non-covalently linked to B doped detonation nanodiamonds (B@DNDs) to yield nanohybrids (B@DNDs-1, B@DNDs-2, B@DNDs-3). The presence of B@DNDs, asymmetry and positive charge resulted in improved PDT with the lowest cell viability being observed for B@DNDs-2 at 5%. The cell viability ranged from 5% to 7% for the nanohybrids compared to 19-26% for Pcs alone., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: A green emission up-conversion carbon-based polymer dots (CPDs) owned excellent photophysical properties and good solubility. Most photosensitizers (PS) are hydrophobic which limits their application in biomedicine. Herein we synthesized and integrated green emitting CPDs into pyropheophorbide-α (PPa) to improve the overall properties of the PS., Material and Methods: The nano-agent was incorporated through amide condensation and electrostatic interaction. The structure, size and morphology of the prepared conjugates were determined by FTIR, TEM, DLS, TGA, 1 HNMR, Uv-vis, and fluorescence spectrophotometry. The dark and light toxicity, as well as cellular uptake, was also monitored on the human esophageal cancer cell line (Eca-109)., Results: Our results illustrate that the conjugation improved the PDT efficacy by increasing the ROS generation. The nano-hybrids showed pH sensitivity as well as good hemocompatibility as the hemolysis ratio was decreased when treated with nano-conjugates. PPa-CPD1 and PPa-CPD2 had the pH response and stronger ability to absorb light and produce fluorescence in an acidic environment (pH 4.0 and pH 5.0) The synthesized nano-hybrids doesnot affect the clotting time. An increase in the absorbance wavelengths was observed. The results of MTT assay showed that dark toxicity was reduced after conjugation., Conclusion: This CPDs-based drug enhanced tumor-inhibition efficiency as well as low dark toxicity in vitro, showing significant application potential for PDT-based treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy has been increasingly used to cope with the alarming problem of cancer. Porphyrins and their derivatives are widely used as Potent Photosensitizers (PS) for PDT. However, the hydrophobicity of porphyrins poses a challenge for their use in clinics, while most of the carbon dots (CDs) are known for good biocompatibility, solubility, and pH sensitivity., Objective: This study aimed to improve the properties/biocompatibility of the pyropheophorbide-α for PDT., Methods: The PPa-CD conjugate was synthesized through covalent interaction using amide condensation. The structure of synthesized conjugate was confirmed by TEM, 1HNMR, and FTIR. The absorption and emission spectra were studied. In vitro, cytotoxicity of the conjugate was examined in human esophageal cancer cell line (Eca-109)., Results: The results showed that the fluorescence of the drug was increased compared to its precursor. CDbased conjugate could generate ROS as well as enhanced biocompatibility by decreasing cytotoxicity. The conjugated drug also showed pH sensitivity in different solutions., Conclusion: The dark toxicity, as well as hemocompatibility, was improved., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Antibiotic resistance is increasing day by day, thereby increase the chances of more infections by resistant bacteria. In this situation, antimicrobial photodynamic therapy (aPDT) is gaining more attraction., Objective: To evaluate the antimicrobial effect of ALA derivatives using photodynamic therapy., Materials and Methods: In this study, we evaluated the aPDT effect of different derivatives of 5-ALA. In vivo and in vitro studies were performed to measure the antimicrobial activity. Different light doses and different concentrations of drugs were used to test anti-bacterial effect of drugs as well as to detect any physiological changes in animal model after the treatment., Results: In vivo studies revealed that ALA-methyl ester, ALA-hexyl ester, and ALA-13A are potent photosensitizers. In vitro studies involved wound healing rate, body weight, and dietary intake were evaluated, and results showed that ALA, ALA-methyl ester, ALA-hexyl ester, and ALA-13A had good anti-bacterial effects, fast healing rate, and no effect on other physical parameters., Conclusion: Photodynamic therapy is increasingly used to treat different types of skin infections caused by bacterial strains. Our studies revealed that ALA-methyl ester, ALA-hexyl ester, and ALA-13A are promising photosensitizers for photodynamic therapy to inhibit the growth of resistant bacterial strains., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chlorophyll a exhibits excellent photosensitive activity in photosynthesis. The unstability limited its application as photoensitizer drug in photodynamic therapy. Here a series of novel chlorophyll a degradation products pyropheophorbide-a derivatives were synthesized and evaluated for lung cancer in PDT. These compounds have strong absorption in 660-670 nm with high molar extinction coefficient, and fluorescence emission in 660-675 nm upon excitation with 410-415 nm light. They all have much higher ROS yields than pyropheophorbide-a, and compound 10 was even higher than [3-(1-hexyloxyethyl)]-pyrophoeophorbide a (HPPH). Distinctive phototoxicity was observed in vitro and the inhibition effect was in light dose-dependent and drug dose-dependent style. They can effectively inhibit the growth of lung tumor in vivo. Among them, compound 8 and 11 have outstanding photodynamic anti-tumor effects without obvious skin photo-toxicity, so they can act as new drug candidates for photodynamic therapy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The development of novel photosensitizers is a challenging task for photodynamic therapy (PDT). Twelve novel photosensitizers (PSs), including porphins (P1-4), chlorins (C1-4) and bacteriochlorins (B1-4) were synthesized. The bacteriochlorins exhibited the longest absorption wavelength (λ max  = 736 nm), which is higher than that of porphins (λ max  = 630 nm) and chlorins (λ max  = 644 nm). In vitro photodynamic activities on Eca-109 human esophageal carcinoma cells were evaluated by standard assays and all PSs showed photodynamic activity. Among them, B2 displayed the highest phototoxicity and the lowest dark toxicity. In addition, B2 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing Eca-109 cells tumor. Therefore, B2 is a powerful and promising antitumor photosensitizer for PDT., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Three novel 17 3 -dicarboxylethyl-pyropheophorbide-a amide derivatives as photosensitizers for photodynamic therapy (PDT) were synthesized from pyropheophorbide-a (Ppa). Their photophysical and photochemical properties, intracellular localization, photocytotoxicity in vitro and in vivo were investigated. All target compounds exhibited low cytotoxicity in the dark and remarkable photocytotoxicity against human esophageal cancer cells. Among them, 1a showed highest singlet oxygen quantum yield. Upon light activation, 1a exhibited significant photocytotoxicity. After PDT treatment, the growth of Eca-109 tumor in nude mice was significantly inhibited. Therefore, 1a is a powerful and promising antitumor photosensitizer for PDT., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A novel 13 1 -pyridine substituted chlorin e 6 derivative (Chlorin A) was synthesized. It has characteristic long wavelength absorption at 664 nm and the emission wavelength at 667 nm. The generation rate of singlet oxygen of this compound is higher than Temoporfin. In vitro, Chlorin A showed higher phototoxicity against the human esophageal cancer cells than Temoporfin while with lower dark-toxicity. Its accumulation effect in mitochondria, lysosomes and endoplasmic reticulum was traced in subcellular localization tests. In flow cytometry obvious apoptosis cells were observed after 2 h irradiation. Significant in vivo photodynamic anti-tumor efficacy was also exhibited on mice bearing esophageal cancer. So Chlorin A could be suggested as a promising anti-tumor drug candidate in photodynamic therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Protoporphyrin IX (PpIX) is used as a photosensitizer in the photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of cancer and is synthesized intracellularly from 5-aminolevulinic acid (5-ALA) precursors. Thirteen novel 5-ALA derivatives were designed and synthesized appropriately with tailored hydrophilicity and lipophilicity. The generation of PpIX was detected and their antitumor activity in vitro and in vivo was also investigated. It was shown that compounds 9b-c, 11b-c and 13a displayed a characteristic long wavelength absorption peak at 593 nm after 5 h incubation in mice fibrosarcoma S180 cells. After being exposed to 600 nm laser light irradiation, these compounds can inhibit cell proliferation in S180 cells in vitro. The growth of S180 cell tumors in Kunming mice was significantly inhibited by these compounds in vivo. Among these compounds, 13a has low dark toxicity and high phototoxicity, which makes it an effective and promising prodrug for PDT.

Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma., (Published by Elsevier Masson SAS.)

This study aimed to investigate the effect of hematoporphyrin dimethylether (HDME)-mediated photodynamic therapy for laser-induced choroidal neovascularization (CNV) in adult Brown Norway rats. HDME was administered via tail vein at 14 d after the laser photocoagulation, and the rats received irradiance with a laser light at 570 nm at 15 min after injection. CNV was evaluated by fundus photography, fundus fluorescein angiography, optical coherence tomography, and hematoxylin and eosin staining. We found that CNV was occurred at 7 d after photocoagulation and reaching peak activity at 14 d after photocoagulation. There is a significant reduction in the total area of the fluorescein leakage and the number of strong fluorescein leakage spots on 7 d after HDME-mediated photodynamic therapy (PDT). The results suggest that HDME-mediated PDT inhibits laser-induced CNV in rats, representing a promising therapy for wet age-related macular degeneration.

Photodynamic therapy (PDT) is a noninvasive therapeutic and promising procedure in cancer treatment and has attracted considerable attention in recent years. In the present paper, 2-piperidinetetraphenylporphyrin derivatives (P1-P3) conjugated with different substituents (Cl, Me, MeO group) at phenyl position were synthesized via nucleophilic substitution of 2-nitroporphyrin copper derivatives with piperidine by refluxing under a nitrogen atmosphere and then demetalization. The combination of 1 H NMR, 13 C NMR and HR-MS was used to elucidate the identities of them. Their photophysical and photochemical properties, intracellular localization, cytotoxicity in vitro and in vivo against QBC-939 cells were investigated. They have absorption at wavelength about 650nm. All synthesized photosensitizers showed low dark cytotoxicity and comparable with that of hematoporphyrin monomethyl ether (HMME). And they were more phototoxic than HMME to QBC-939 cells in vitro. In bearing QBC-939 tumor BALB/c nude mice, when it treated with 5mg/kg dose of PS and laser light (650nm, 100J/cm 2 , 180mW/cm 2 ), the growth of tumor was inhibited compared to the control group. Among them, P3 exhibited better photodynamic antitumor efficacy on BALB/c nude mice at lower concentration. These results indicate that P3 is a new potential antitumor photosensitizer in photodynamic therapy and deserves further investigation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A series of β-alkylaminoporphyrins conjugated with different amines at β position (D1-D3) or with electron-donating and electron-withdrawing substituents at phenyl position (D4-D6) were synthesized. Their photophysical and photochemical properties, intracellular localization, photocytotoxicities in vitro and vivo were also investigated. All target compounds exhibited no cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells. Among them, D6 showed the highest phototoxicity and the lowest dark toxicity, which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor photosensitizer for photodynamic therapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Photodynamic therapy is a minimally invasive and promising new method in cancer treatment and has attracted considerable attention in recent years. An ideal photosensitizer is a crucial element to photodynamic therapy. In the present paper, a novel porphyrin derivative, 5, 10, 15, 20-tetrakis (5-(pyrrolidin-1-yl) pentyl) porphin (TPPP) was synthesized. Its spectroscopic and physicochemical properties, therapeutic efficacy as a photosensitizer in photodynamic therapy for human bladder cancer in vitro and in vivo were investigated. TPPP had strong absorption at 648nm (ε=1.75×10(4)M(-1)cm(-1)), and two fluorescence emission peaks at 652nm and 718nm. PDT with TPPP showed low dark toxicity and high phototoxicity to human bladder cancer T24 cells in vitro. In bearing T24 tumor nude mice, the growth of tumor was significantly inhibited by combining use of 5mg/kg TPPP with 100J/cm(2) (650nm, 180mW/cm(2)) laser irradiation at 3h following injection of TPPP. The antitumor effect was also confirmed with histopathological assay. The histopathological study results revealed that PDT using TPPP and 100J/cm(2) (650nm, 180mW/cm(2)) laser irradiation induced tumor cells shrunken and necrotic. These results indicate that TPPP is useful as a new photosensitizer in PDT for cancer, and deserves further investigation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This paper reports the antitumor activity of a chlorophyll-a derivative, 2-[1-hydroxyethyl]-2-devinylpyropheophorbide-a (HEPa). Photophysical characteristics of HEPa were measured. And its cytotoxicity, intracellular localization, biodistribution, efficiency of photodynamic therapy (PDT), histological analysis were investigated using human bile duct carcinoma cells (QBC-939) and QBC-939 tumor bearing BABL/c nude mice as animal model. The results showed that HEPa was localized mainly within the cytoplasmic region and partially in lysosome. Biodistribution of HEPa in QBC-939 tumor bearing BABL/c nude mice showed its fast rate of clearance and high tumor selectivity. In vitro, HEPa had low dark toxicity and high photoxicity against QBC-939 cells. The inhibition rate of QBC-939 tumor could increase up to 92.3%, and H&E staining confirmed that HEPa could cause serious damage to the tumor with light dose of 100J/cm(2), implying that HEPa has potential to be a new antitumor candidate for photodynamic therapy (PDT)., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A novel porphyrin derivative, 5, 10, 15, 20-tetrakis (5-morpholinopentyl)-21H, 23H-Porphin (MPP, 4) and its photophysical characteristics, therapeutic efficacy of photodynamic therapy (PDT) in vitro and in vivo, tumor selectivity, and clearance from normal tissues were investigated here. MPP has strong absorption at relatively long wavelength (λmax = 648 nm, molar absorption coefficient ε ∼ 17,200 M(-1)cm(-1)) and can emit strong fluorescence at 653 and 718 nm. When administered to the animal tumor models by tail vein injection, MPP was capable of accumulating in the tumor site, as examined in vivo with the fluorescence signal of MPP. By the combination of MPP and a 650-nm laser irradiation, the viability of T24 cells could decrease by 4.37 %, and inhibition rate of T24 tumor could increase up to 91.21 % compared with control group, demonstrating the potential of MPP as an effective photosensitizer in PDT for tumor treatment.

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

Purpose: Bacteriochlorin derivatives are promising photosensitive agents for photodynamic therapy (PDT) of tumors. In the current study, the photodynamic activity of a novel bacteriochlorin derivative, cis-2, 3, 12, 13-tetracarboxymethyl-5, 10, 15, 20-tetraphenyl bacteriochlorin (TCTB), was evaluated both in vitro and in vivo., Methods: Physicochemical characteristics of the novel photosensitizer were measured. The efficiency of TCTB-PDT in vitro was analyzed by MTT assay, clonogenic assay and in situ trypan blue exclusion test. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The accumulation of TCTB in human malignant tumor cells was measured by fluorescence spectrometer, and the pathway of cell death was analyzed by flow cytometry. S180 tumor model was used to evaluate the anti-tumor effects of TCTB-PDT. And histopathological study was also used to confirm the anti-tumor effect., Results: TCTB shows a singlet oxygen quantum yield of 0.56 and displays a characteristic long wavelength absorption peak at 732 nm. The accumulation of TCTB increased in time-dependent manner, and it was found in cytoplasm and nuclear membranes. In vitro PDT using TCTB and Nd:YAG laser showed drug concentration-, laser dose-dependent cytotoxicity to human esophageal cancer Eca-109 cells. In mice bearing osteosarcoma S180 tumors, the combined use of 10 mg/kg TCTB and 120 J/cm(2) showed superior anti-tumor activity. Histology examination of tumor tissues revealed that PDT using TCTB and the Nd:YAG laser induced tumor cells shrunken and necrotic., Conclusion: In in vitro and in vivo studies, we found that TCTB has excellent anti-tumor effect. It suggests that TCTB is a potential photosensitizer of PDT for cancer.

Chlorin derivatives are promising photosensitive agents for photodynamic therapy (PDT) of tumors. The aim of the current study is to investigate the PDT therapeutic effects of a novel chlorin-based photosensitizer, meso-tetra[3-(N,N-diethyl)aminomethyl-4-methoxy]phenyl chlorin (TMPC) for gliomas in vitro and in vivo. Physicochemical characteristics of TMPC were recorded by ultraviolet visible spectrophotometer and fluorescence spectrometer. The rate of singlet oxygen generation of TMPC upon photo-excitation was detected by using 1,3-diphenylisobenzofuran (DPBF). The accumulation of TMPC in gliomas U87 MG cells was measured by fluorescence spectrometer. The efficiency of TMPC-PDT in vitro was analyzed by MTT assay and clonogenic assay. The biodistribution and clearance of TMPC were determined by fluorescence measuring. Human gliomas U87 MG tumor-bearing mice model was used to evaluate the antitumor effects of TMPC-PDT. TMPC shows a singlet oxygen generation rate of 0.05 and displays a characteristic long wavelength absorption peak at 653 nm (ε = 15,400). The accumulation of TMPC increased with the increase of incubation time. In vitro, PDT using TMPC and laser showed laser dose- and concentration-dependent cytotoxicity to U87 MG cells. In U87 MG tumor-bearing mice, TMPC-PDT significantly reduced the growth of the tumors. Both in vitro and in vivo, TMPC showed little dark toxicity. In vitro and in vivo studies, it found that TMPC has excellent antitumor activities. It suggests that TMPC is a potential photosensitizer of photodynamic therapy for cancer.

Purpose: Photodynamic therapy (PDT) is a promising noninvasive treatment, which has been approved by the US Food and Drug Administration for the treatment of localized tumors. With the aim to select an appropriate photosensitizer for tumor treatment in PDT, the antitumor effect of a novel chlorin-based photosensitizer, meso-tetra (3-morphlinomethyl-4-methoxyphenyl) chlorin (TMMC) (Fig. 1a) on two types of human malignant tumor cells in vitro and a esophageal cancer model in nude mice, was evaluated in the present paper. Fig. 1 Chemical structure and spectrum properties of TMMC in DMF. a Chemical structure of TMMC in DMF. b UV-Vis absorption spectrum of TMMC in DMF. Its maximum absorbance is at 423 nm, and at 527, 555, 600, 655 nm and 712 nm, also it has absorption. c Emission spectrum of TMMC, which was excited at 514 nm, and its peaks were at 656 and 720 nm. d The matrix of excitation and emission spectra (Ex: 300-550 nm, Em: 600-780 nm), Methods: The efficiency of TMMC-PDT in vitro was analyzed by MTT assay and clonogenic assay. The intracellular distribution of photosensitizers was detected with laser scanning confocal microscopy. The accumulation of TMMC in human malignant tumor cells was measured by Fluorescence Spectrometer, and the pathway of cell death was analyzed by flow cytometry. Eca-109 tumor model was used to evaluate the antitumor effects of TMMC-mediated PDT. And the singlet oxygen quantum yield of TMMC was also measured using DPBF as substrate., Results: TMMC shows a singlet oxygen quantum yield of 0.59 and displays a characteristic long wavelength absorption peak at 655 nm. The accumulation of TMMC increased in time-dependent manner, and it was found in cytoplasm and nuclear membranes. TMMC-PDT induced cell death by the major death pathway of necrosis and significantly reduced the growth of Eca-109 tumors in nude mice (180 mW/cm(2), 120 J/cm(2))., Conclusion: The studies suggest that TMMC is an effective photosensitizer for PDT to tumors. Therefore, TMMC has great potentials for tumor treatment in PDT and deserves further investigation.

Photodynamic therapy (PDT) is a promising new treatment for cancer that has been recently accepted clinically. PDT is based on the administration of tumor-localizing photosensitizers (PSs), followed by exposing the neoplastic area to the light absorbed by the PS. In this article, a novel anticancer nanofiber membrane containing purpurin-18 (0.1%) was successfully prepared. The thickness of membrane was 0.028 mm, and the average fiber diameter was around 357 nm by scanning electron microscope (SEM). It was indicated that purpurin-18 possessed excellent compatibility with PLLA from FTIR spectrum. The physical properties of fiber membrane were also characterized by Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD). Cell morphology and the interaction between cells and nanofibers were studied by SEM. The results showed that both SMMC 7721 and ECA109 cells can adhere and spread on the surface of the polymer nanofiber, and both cells can interact and integrate well with the surrounding fibers. The efficacy of PDT was determined by MTT assays. The results showed that the cells were killed immediately after PDT and purpurin-18 had no different efficacy to different cancer cell lines. In summary, the PS-loaded PLLA nanofibers were prepared successfully, and the SMMC 7721 and ECA109 cells could be inhibited and killed through photodynamic therapy.

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer play key roles in the treatment efficacy. In this study, a novel photosensitizer, Chlorin-H [-13,15-N-(cyclohexyl)cycloimide] which displayed a characteristic long wavelength absorption peak at 698nm was synthesized. Following flash photolysis with 355nm laser, Chlorin-H is potent to react with O(2) and then produce (1)O(2). This finding indicates that Chlorin-H takes its effects through type II mechanism in PDT. Generally, Chlorin-H is localized in mitochondria and nucleus of cell. After light irradiation with 698nm laser, it can kill many types of cell, inhibit cell proliferation and colony formation, suppress cancer cell invasiveness and trigger apoptosis via the mitochondrial pathway in A549 cells in vitro. In addition, Chlorin-H-PDT can destroy A549 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following Chlorin-H-PDT. The results showed that it either increased or decrease. Among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. Silencing of TNFSF13 caused by RNA interference decreased the susceptibility of A549 cells to Chlorin-H-PDT. In general, Chlorin-H is an effective antitumor photosensitizer in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new photosensitizers., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 microM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

A novel magnetic nanocarrier was strategically designed and successfully prepared. Phot0sensitizer 2, 7, 12, 18 - tetramethyl - 3, 8 - di -(1 - propoxyethyl)- 13, 17 - bis - (3 - hydroxypropyl) porphyrin (PHPP) was encapsulated into polylactic acid (PLA)- coated Fe304 nanoparticles. The diameter of nanocarrier is 30 - 50 nm by transmission electron micrograph (TEM). The encapsulation efficiency of photosensitizer is 27.98% calculated from UV - vis absorption spectra. The nanocarrier shows obvious photocytotoxic activity to Hela299 tumor cells in vitro. [ABSTRACT FROM AUTHOR]