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A pH-responsive zinc (II) metalated porphyrin for enhanced photodynamic/photothermal combined cancer therapy; 一种用于增强光动力/光热协同肿瘤治疗的酸性 刺激响应锌(II)金属卟啉化合物;
摘要： The acidic tumor microenvironment is triggered by glycolysis in hypoxic condition, which can motivate the pH-responsive system to build certain triggers for efficiently tumor-targeted phototherapy. Additionally, the metalated porphyrin structures are widely studied in biomedical applications due to the favorable properties of high singlet oxygen quantum yield as well as strong fluorescence imaging ability. Herein, a pH-responsive zinc (II) metalated porphyrin (P-4) was designed and synthesized for amplifying cancer photodynamic/photothermal therapy with excellent fluorescence quantum yield (67.4%), superb singlet oxygen quantum yield (84.3%) and desired photothermal conversion efficiency (30.0%). In vitro, the self-assembled P-4 nanoparticles can specifically target to lysosome subcellular site and realize protonated process of dibutaneaminophenyl (DBAP) groups with high photo toxicity. Under single 660 nm laser illumination, the tumor can be ablated completely with no side effects in vivo. This work demonstrates that the pH-responsive P-4 nanoparticles provide a new avenue for highly efficient cancer combination therapy.
关键词： porphyrin,pH-responsive,NIR absorbance,photothermal therapy,photodynamic therapy
更新于2025-11-14 15:29:11
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Green Synthesis of Carrier-Free Curcumin Nanodrugs for Light-activated Breast Cancer Photodynamic Therapy
摘要： Photodynamic therapy (PDT) is a promising procedure for breast cancer therapy. Curcumin (Cur), a hydrophobic polyphenol derived from the spice turmeric, has been considered as a potential photosensitizer for PDT with evoked immune response, excellent safety, and low cost. However, the translation of curcumin in clinical cancer therapy suffers from an insufficient therapeutic dose in tumor tissues due to its poor solubility and low bioavailability. In this study, carrier-free curcumin nanodrugs (Cur NDs) were prepared without using any toxic solvents through a facile and green reprecipitation method. Cur NDs exhibited distinct optical properties, light-sensitive drug release behavior, resulting in increased reactive oxygen species (ROS) generation and PDT efficacy on breast cancer cells compared with free Cur. Furthermore, cell apoptosis during Cur-based PDT was concomitant with the activation of the ROS-mediated JNK/caspase-3 signaling pathway. Overall, our carrier-free Cur nanodrugs may be promising candidates for facilitating the efficacy and safety of PDT against breast cancer.
关键词： Carrier-free,Curcumin,Light-responsive drug release,Breast cancer,Photodynamic therapy
更新于2025-11-14 15:26:12
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Antimicrobial-Peptide-Conjugated MoS2 Based Nanoplatform for Multimodal Synergistic Inactivation of Superbugs
摘要： Development of new antibacterial therapeutics material is becoming increasingly urgent due to the huge threat of superbugs, which are responsible for more than half million death each year in this world. Here, we report the development of novel nano-biomaterial based on melittin antimicrobial peptide (AMP) attached transition metal dichalcogenide MoS2 based theranostic nanoplatform. Reported nanoplatform has capability for targeted identification and synergistic inactivation of 100% multidrug-resistant superbugs by combined photo thermal therapy (PTT), photodynamic therapy (PDT) and AMP process. A novel approach for the design of melittin antimicrobial peptide attached MoS2 based nanoplatform is reported, which emits very bright and photo stable fluorescence. It also generates heat as well as reactive oxygen species (ROS) in the presence of 670 nm near infrared light, which allow it to be used as PTT & PDT agent. Due to the presence of AMP, multifunctional AMP exhibits significantly improved antibacterial activity for superbugs via multimodal synergistic killing mechanism. Reported data demonstrate that nanoplatforms are capable of identification of multidrug-resistant superbugs via luminescence imaging. Experimental results show that it is possible to kill only ~45% of superbugs via MoS2 nanopaltform based on PTT & PDT processes together. On the other hand, killing of less than 10% of superbugs is possible using melittin antimicrobial peptide alone. Whereas, 100% Methicillin-resistant Staphylococcus aureus (MRSA), drug resistance Escherichia coli (E. coli) and drug resistance Klebsiella pneumoniae (KPN) superbugs can be killed using antimicrobial peptide attached MoS2 QDs, via synergistic killing mechanism. Mechanisms for possible synergistic killing of multidrug-resistant superbugs have been discussed.
关键词： theranostic transition metal dichalcogenide,photodynamic therapy,multimodal therapy for multidrug-resistant superbugs,Melittin antimicrobial peptide attached MoS2 based nanoplatform,photo thermal therapy
更新于2025-09-23 15:23:52
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Development of Photo-Activated ROS-Responsive Nanoplatform as a Dual-Functional Drug Carrier in Combinational Chemo-Photodynamic Therapy
摘要： Dual functional drug carrier has been a modern strategy in cancer therapy because it is a platform to elicit additive and synergistic effects through combination therapy. Photo-activated external stimuli such as reactive oxygen species (ROS) also ensure adequate drug delivery in a precise temporal and spatial manner. However, current ROS-responsive drug delivery systems usually require tedious synthetic procedures. A facile one-pot approach has been reported herein, to obtain self-assembled polymeric nanocarriers (NCs) for simultaneous paclitaxel (PTX)- and Rose Bengal (RB)-loading to achieve combined chemo-photodynamic therapy and controlled drug release in responsive to a light-induced ROS stimulus. To encapsulate these hydrophobic and hydrophilic drugs, chitosan (CTS), branched polyethylenimine (bPEI) and polyvinyl alcohol (PVA) were selected and fabricated into nanoblended matrices through an oil-in-water emulsion method. The amphiphilic properties of CTS permit simultaneous entrapment of PTX and RB, while the encapsulation efficiency of RB was further improved by increasing the amount of short-chain bPEI. During the one-step assembly process, bovine serum albumin (BSA) was also added to condense the cationic tripolymer mixtures into more stable nanocarriers (BNCs). Hyaluronic acid (HA) was subsequently grafted onto the surface of BNCs through electrostatic interaction, leading to the formation of HA-BSA/CTS/PVA/bPEI-blended nanocarriers (HBNCs) to achieve an efficient prostate-cancer-cell uptake. Importantly, in response to external light irradiation, HBNCs become destabilized owing to the RB-mediated photodynamic action. It allows an on-demand dual-payload release to evoke a simultaneous photodynamic and chemo treatment for cancer cell eradication. Thus, HBNCs present a new promising approach that exhibits a specific vulnerability to RB-induced photosensitization. The consequent dual-cargo release is also expected to successfully combat cancer through a synergistic anti-tumor effect.
关键词： ROS-responsive,photodynamic therapy,nanocarrier,chemotherapy,combined therapy
更新于2025-09-23 15:23:52
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Intratumorally Injected Photothermal Agent-Loaded Photodynamic Nanocarriers for Ablation of Orthotopic Melanoma and Breast Cancer
摘要： Traditional chemotherapy of cancers may lead to serious adverse reactions due to little drug distribution in tumors. Here, a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) was used for local treatment of orthotopic melanoma and breast cancer via intratumoral (i.t.) injection of photothermal agent-loaded photodynamic nanocarriers. A hydrophobic derivative of indocyanine green, DCC, was synthesized and entrapped into a pH-sensitive photosensitizer-core copolymer, PDCZP, to form DCC@PDCZP. The nanocarriers showed remarkable fluorescence, high singlet oxygen quantum yields, and strong photothermal effect. Flow cytometry suggested that the nanocarriers were efficiently internalized by cancer cells. Near infrared thermal imaging and fluorescence self-imaging showed that the i.t. injected DCC@PDCZP mainly remained in the tumors but the intravenous (i.v.) nanocarriers were distributed a little. One i.t. injection of DCC@PDCZP was enough to ablate the orthotopic B16-F10 and 4T1 mouse tumors under 830 nm and 660 nm irradiation at 4 hours post-injection. More importantly, no local recurrences were found though scabs were formed at 9 days post-treatment. The major anticancer mechanisms included improvement of cancer cell necrosis due to hyperthermia, inhibition of neovascularization, and enhancement of cell apoptosis. The i.t. injection of PTT/PDT nanoformulations is thus a promising local treatment of superficial tumors.
关键词： zinc phthalocyanine,intratumoral injection,melanoma,indocyanine green,breast cancer,photodynamic therapy,photothermal therapy
更新于2025-09-23 15:23:52
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Oxidative stress generated by irradiation of a zinc(II) phthalocyanine induces a dual apoptotic and necrotic response in melanoma cells
摘要： Melanoma is an aggressive form of skin carcinoma, highly resistant to traditional therapies. Photodynamic therapy (PDT) is a non-invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. In this work we evaluated the effect of a cationic zinc(II) phthalocyanine (Pc13) as photosensitizer on a panel of melanoma cells. Incubation with Pc13 and irradiation induced a concentration and light dose-dependent phototoxicity. In order to study the mechanism underlying Pc13-related cell death and to compare the effect of different doses of PDT, the most sensitive melanoma B16F0 cells were employed. By confocal imaging we showed that Pc13 targeted lysosomes and mitochondria. After irradiation, a marked increase in intracellular reactive oxygen species was observed and a complete protection from Pc13 phototoxicity was reached in the presence of the antioxidant trolox. Acridine orange/ethidium bromide staining showed morphological changes indicative of both apoptosis and necrosis. Biochemical hallmarks of apoptosis, including a significant decrease in the expression levels of Bcl-2, Bcl-xL and Bid and mitochondrial membrane permeabilization, were observed at short times post irradiation. The consequent release of cytochrome c to cytosol and caspase-3 activation led to PARP-1 cleavage and DNA fragmentation. Simultaneously, a dose dependent increase of lactate dehydrogenase in the extracellular compartment of treated cells revealed plasma membrane damage characteristic of necrosis. Taken together, these results indicate that a dual apoptotic and necrotic response is triggered by Pc13 PDT-induced oxidative stress, suggesting that combined mechanisms of cell death could result in a potent alternative for melanoma treatment.
关键词： Necrosis,Mitochondrial membrane permeabilization,Apoptosis,Reactive oxygen species,Photodynamic therapy,Cationic phthalocyanine
更新于2025-09-23 15:23:52
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Impact of photodynamic therapy versus ultrasonic scaler on gingival health during treatment with orthodontic fixed appliances
摘要： Objectives: Poor oral hygiene during treatment with fixed appliances results in plaque accumulation. The presence of bacteria in the gingival crevice triggers an inflammatory reaction in the gingival tissues. The aim of this study was to compare the impact of two preventive treatments, photodynamic therapy (PDT), and ultrasonic scaler (US), on gingival health in patients under fixed orthodontic treatment. Methods: Twenty orthodontic patients were randomly allocated to two groups: PDT or US. Each group received seven sessions [days 0, 15, 30, 45, 90 (3-months follow-up), 180 (6-months follow-up), 270 (9-months follow-up)] of experimental interventions, and clinical parameters [Plaque index(PI); gingival index(GI); probing depth(PD)], periodontopathogens [Aggregatibacter actinomycetemcomitans; Porphyromonas gingivalis; Prevotella intermedia; Micromonas micros; Fusobacterium nucleatum; Tannerella forsythia; Campylobacter rectus; Eikenella corrodens; Capnocytophaga sp.] and protein markers [IL-1b;IL-1ra;IL-6;IL-10; TNF-a;FGF-2/FGF basic] were monitored at baseline and at 3, 6, and 9 months. ANOVA, Student’s t-test with Bonferroni correction and ANOVA with multiple rank test were used to identify differences between groups (P < 0.05). Results: Clinical assessments [PI, GI, and PD] yielded no differences (P > 0.05) between groups, which showed a major decrease at the start of the trial. Reductions in total colony forming units (log CFU reduction) were observed with both treatments, although to a greater extent in the PDT group, but with no differences between groups (P > 0.05). Similar reductions in log CFU counts of P. gingivalis, P. intermedia, and F. nucleatum were observed in both groups (P > 0.05). The two groups also showed similar trends for inflammatory mediators with decreased levels of IL-1b, IL-10, and TNF-a, whereas IL-6 and IL-1ra levels remained stable and those of FGF-2 were increased after both interventions, with no differences (P > 0.05) between groups. Conclusion: Both PDT and US methods proved similar effectiveness for the treatment of gingival inflammation induced by fixed orthodontic appliances.
关键词： photodynamic therapy,cytokines,ultrasonic scaler,orthodontic treatment,gingival inflammation,periodontopathogens
更新于2025-09-23 15:23:52
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Dendrimeric nanoparticles for two-photon photodynamic therapy and imaging: synthesis, photophysical properties and cytotoxicity under two-photon irradiation in the NIR
摘要： The synthesis and the photophysical properties of a new class of fully organic monodisperse nanoparticles for combined two-photon imaging and photodynamic therapy are described. The design of such nanoparticle is based on the covalent immobilization of a dedicated quadrupolar dye - which combine large two-photon absorbing (2PA) properties, fluorescence and singlet oxygen generation ability - in a phosphorous-based dendrimeric architecture. Firstly, a bifunctional quadrupolar dye bearing two different grafting moieties, a phenol function and an aldehyde function, was synthesized. It was then covalently grafted through its phenol function to a phosphorus-based dendrimer scaffold of generation 1. The remaining aldehyde functions were then used to carry on the dendrimer synthesis up to generation 2 introducing finally at its periphery 24 water-solubilizing triethyleneglycol chains. A dendrimer confining 12 photoactive quadrupolar units in its inner scaffold and showing water solubility was thus obtained. Interestingly, the G1 and G2 dendrimers retain some fluorescence as well as significant singlet oxygen production efficiencies while they were found to show very high 2PA cross-sections in a broad range of the NIR biological spectral window. Hydrophilic dendrimer G2 was tested in vitro on breast cancer cells, first in one- and two-photon microscopy, which allowed for visualization of their cell internalization, then in two-photon photodynamic therapy. While being non-toxic in the dark and, more importantly, under daylight exposition, dendrimer G2 proved to be very efficient cell death inducer only under two-photon irradiation in the NIR.
关键词： photophysics,photodynamic therapy,dendrimers,imaging,fluorescence
更新于2025-09-23 15:23:52
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Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway
摘要： Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 μmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.
关键词： iTRAQ,Hypocrellin A,Proteomic,Reactive oxygen species,LC–MS/MS,Photodynamic therapy
更新于2025-09-23 15:23:52
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Blue Copper Peroksidase and Phthalocyanine Conjugate: Synthesis, Characterization and Applications
摘要： Trametes versicolor can degrade barks as a source for carbon necessity. Therefore it secretes lignin peroxidase, mangan peroxidase and laccase. The laccase enzyme was produced high yield at pH and glucose concentration 5 and 10 gL-1, respectively. In optimized medium, the enzyme activity was between 200-250 UL-1 when inducer was absent. It was seen that the activity reached 400 UL-1 when phenol used as an inducer. The molecular weight of purified laccase was found 80 kDa with SDS-PAGE and kinetic constant Km and Vmax values for ABTS were determined 3.66x10-4 μM and 1652 UL-1, respectively. Hence, due to these properties, these enzymes are widely used in industrial areas free or immolized. Laccase enzyme decolorization of 6 different dyes was carried out. A decolorization capacity of 50-99% was achieved by cultivation in 20 days using a beginning dye concentration of 20 ppm. The removal of color with active enzyme is obtained around 90%. Also laccase enzyme was conjugated amine functionalized low symmetrically phthalocyanine. This conjugate was examined both photodynamic therapy and chemosensor application. This conjugate fluorescence had a quantum yield of 0.32 (lifetime 3.59 ns) and generates efficiently singlet oxygen (quantum yield 0.4). The conjugate was successfully photodamage displayed in HeLa and HuH-7 cells in photodynamic therapy application. These results indicate that conjugate represent interesting agent with potential applications in photodynamic therapy. In addition that the chemosensor behavior of this compound to different metal ions has been studied and this conjugate display as fluorescence chemosensor for determination of Fe3+ions.
关键词： Conjugate,Zinc phthalocyanine,Metal Sensor,Laccase,Photodynamic Therapy
更新于2025-09-23 15:23:52