scholarly journals Methylene-Blue-Encapsulated Liposomes as Photodynamic Therapy Nano Agents for Breast Cancer Cells

Nanomaterials ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 14 ◽  
Author(s):  
Po-Ting Wu ◽  
Chih-Ling Lin ◽  
Che-Wei Lin ◽  
Ning-Chu Chang ◽  
Wei-Bor Tsai ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Light Exposure ◽  
Drug Carriers ◽  
Ros Generation ◽  
Enhanced Permeability And Retention ◽  
Zwitterionic Polymer

Methylene blue (MB) is a widely used dye and photodynamic therapy (PDT) agent that can produce reactive oxygen species (ROS) after light exposure, triggering apoptosis. However, it is hard for the dye to penetrate through the cell membrane, leading to poor cellular uptake; thus, drug carriers, which could enhance the cellular uptake, are a suitable solution. In addition, the defective vessels resulting from fast vessel outgrowth leads to an enhanced permeability and retention (EPR) effect, which gives nanoscale drug carriers a promising potential. In this study, we applied poly(12-(methacryloyloxy)dodecyl phosphorylcholine), a zwitterionic polymer-lipid, to self-assemble into liposomes and encapsulate MB (MB-liposome). Its properties of high stability and fast intracellular uptake were confirmed, and the higher in vitro ROS generation ability of MB-liposomes than that of free MB was also verified. For in vivo tests, we examined the toxicity in mice via tail vein injection. With the features found, MB-liposome has the potential of being an effective PDT nano agent for cancer therapy.

scholarly journals Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1760 ◽  
Author(s):  
Michy ◽  
Massias ◽  
Bernard ◽  
Vanwonterghem ◽  
Henry ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Photodynamic Therapy ◽  
Side Effects ◽  
Laser Light ◽  
Light Exposure ◽  
Gynecological Cancer ◽  
Ovarian Cancer Cells ◽  
Pharmacokinetic Studies

Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and phototoxicity of free verteporfin and NLC-verteporfin were studied in vitro in human ovarian cancer cell lines cultured in 2D and 3D-spheroids, and biodistribution and photodynamic therapy were evaluated in vivo in mice. Both molecules were internalized in ovarian cancer cells and strongly inhibited tumor cells viability when exposed to laser light only. In vivo biodistribution and pharmacokinetic studies evidenced a long circulation time of NLC associated with efficient tumor uptake. Administration of 2 mg.kg−1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. In contrast, laser light exposure of tumors after intravenous administration of NLC-verteporfin (8 mg.kg−1) significantly inhibited tumor growth without visible toxicity. NLC-verteporfin thus led to efficient verteporfin vectorization to the tumor site and protection from side-effects, providing promising therapeutic prospects for photodynamic therapy of cancer.

scholarly journals Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2190
Author(s):  
Howard Kim ◽  
Mi Woon Kim ◽  
Young-IL Jeong ◽  
Hoe Saeng Yang
Keyword(s):  
Cervical Cancer ◽  
Photodynamic Therapy ◽  
Hela Cells ◽  
Folate Receptor ◽  
Chlorin E6 ◽  
Ros Generation ◽  
Cervical Cancer Cells ◽  
Poly Ethylene

The aim of this study was to fabricate a reactive oxygen species (ROS)-sensitive and folate-receptor-targeted nanophotosensitizer for the efficient photodynamic therapy (PDT) of cervical carcinoma cells. Chlorin e6 (Ce6) as a model photosensitizer was conjugated with succinyl β-cyclodextrin via selenocystamine linkages. Folic acid (FA)-poly(ethylene glycol) (PEG) (FA-PEG) conjugates were attached to these conjugates and then FA-PEG-succinyl β-cyclodextrin-selenocystamine-Ce6 (FAPEGbCDseseCe6) conjugates were synthesized. Nanophotosensitizers of FaPEGbCDseseCe6 conjugates were fabricated using dialysis membrane. Nanophotosensitizers showed spherical shapes with small particle sizes. They were disintegrated in the presence of hydrogen peroxide (H2O2) and particle size distribution changed from monomodal distribution pattern to multimodal pattern. The fluorescence intensity and Ce6 release rate also increased due to the increase in H2O2 concentration, indicating that the nanophotosensitizers displayed ROS sensitivity. The Ce6 uptake ratio, ROS generation and cell cytotoxicity of the nanophotosensitizers were significantly higher than those of the Ce6 itself against HeLa cells in vitro. Furthermore, the nanophotosensitizers showed folate-receptor-specific delivery capacity and phototoxicity. The intracellular delivery of nanophotosensitizers was inhibited by folate receptor blocking, indicating that they have folate-receptor specificity in vitro and in vivo. Nanophotosensitizers showed higher efficiency in inhibition of tumor growth of HeLa cells in vivo compared to Ce6 alone. These results show that nanophotosensitizers of FaPEGbCDseseCe6 conjugates are promising candidates as PDT of cervical cancer.

scholarly journals Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy

2021 ◽  
Author(s):  
Xiaoqing Yi ◽  
Jingjing Hu ◽  
Jun Dai ◽  
Xiaoding Lou ◽  
Zujin Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Continuous Light ◽  
Light Irradiation ◽  
Fluorescence Signal ◽  
Aggregation State ◽  
Aggregation Induced Emission ◽  
Dual Stage

<p>Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N<sub>3</sub>) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L<sub>1</sub>, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L<sub>2</sub>, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both <i>in vivo</i> and <i>in vitro</i> studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.<br></p>

scholarly journals Multifunctional AIE iridium (III) photosensitizer nanoparticles for two-photon-activated imaging and mitochondria targeting photodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuzi Cai ◽  
Kang-Nan Wang ◽  
Wen Ma ◽  
Yuanyuan Yang ◽  
Gui Chen ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Tissue Imaging ◽  
Ros Generation ◽  
Generation Efficiency ◽  
Deep Tissue ◽  
Two Photon ◽  
Mitochondria Targeting

AbstractDeveloping novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.

scholarly journals Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy

2021 ◽  
Author(s):  
Xiaoqing Yi ◽  
Jingjing Hu ◽  
Jun Dai ◽  
Xiaoding Lou ◽  
Zujin Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Continuous Light ◽  
Light Irradiation ◽  
Fluorescence Signal ◽  
Aggregation State ◽  
Aggregation Induced Emission ◽  
Dual Stage

<p>Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N<sub>3</sub>) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L<sub>1</sub>, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L<sub>2</sub>, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both <i>in vivo</i> and <i>in vitro</i> studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.<br></p>

scholarly journals Methylene Blue-Based Nano and Microparticles: Fabrication and Applications in Photodynamic Therapy

Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3955
Author(s):  
Dong-Jin Lim
Keyword(s):  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Textile Industry ◽  
In Vivo Studies ◽  
Future Perspective ◽  
Pharmacological Properties ◽  
Hydrophilic Nature ◽  
Recent Trends

Methylene blue (MB) has been used in the textile industry since it was first extracted by the German chemist Heinrich Caro. Its pharmacological properties have also been applied toward the treatment of certain diseases such as methemoglobinemia, ifosfamide-induced encephalopathy, and thyroid conditions requiring surgery. Recently, the utilization of MB as a safe photosensitizer in photodynamic therapy (PDT) has received attention. Recent findings demonstrate that photoactivated MB exhibits not only anticancer activity but also antibacterial activity both in vitro and in vivo. However, due to the hydrophilic nature of MB, it is difficult to create MB-embedded nano- or microparticles capable of increasing the clinical efficacy of the PDT. This review aims to summarize fabrication techniques for MB-embedded nano and microparticles and to provide both in vitro and in vivo examples of MB-mediated PDT, thereby offering a future perspective on improving this promising clinical treatment modality. We also address examples of MB-mediated PDT in both cancer and infection treatments. Both in-vitro and in-vivo studies are summarized here to document recent trends in utilizing MB as an effective photosensitizer in PDT. Lastly, we discuss how developing efficient MB-carrying nano- and microparticle platforms would be able to increase the benefits of PDT.

scholarly journals Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy

2021 ◽  
Author(s):  
Xiaoqing Yi ◽  
Jingjing Hu ◽  
Dajung Jun ◽  
Xiaoding Lou ◽  
Zujin Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Continuous Light ◽  
Light Irradiation ◽  
Fluorescence Signal ◽  
Aggregation State ◽  
Aggregation Induced Emission ◽  
Dual Stage

<p>Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N<sub>3</sub>) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L<sub>1</sub>, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L<sub>2</sub>, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both <i>in vivo</i> and <i>in vitro</i> studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.<br></p>

Self-guiding Polymeric Prodrug Micelles with Two AIE Photosensitizers for Enhanced Chemo-Photodynamic Therapy

2020 ◽  
Author(s):  
Xiaoqing Yi ◽  
Xiaoding Lou ◽  
Zujin Zhao ◽  
Fan Xia ◽  
Ben Zhong Tang
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Continuous Light ◽  
Polymeric Micelle ◽  
Light Irradiation ◽  
Fluorescence Signal ◽  
Aggregation State ◽  
Dual Stage

<p>Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N<sub>3</sub>) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L<sub>1</sub>, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L<sub>2</sub>, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both <i>in vivo</i> and <i>in vitro</i> studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.</p>

scholarly journals Methylene Blue-Mediated Photodynamic Therapy Induces Macrophage Apoptosis via ROS and Reduces Bone Resorption in Periodontitis

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Chunlan Jiang ◽  
Wenyi Yang ◽  
Chengyi Wang ◽  
Wei Qin ◽  
Jiajun Ming ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Bone Resorption ◽  
Laser Irradiation ◽  
Alveolar Bone ◽  
Fluorescence Probe ◽  
Periodontal Tissues ◽  
Macrophage Apoptosis

Aim. To investigate whether methylene blue-mediated photodynamic therapy (MB-PDT) can affect the “fate” of macrophages in vitro or in periodontitis tissues and to explore the potential mechanism. Methods. For in vitro treatments, THP-1 macrophages were divided into three experimental groups: C/control, no treatment; MB, methylene blue treatment; and MB-PDT, MB and laser irradiation treatment. Then, apoptosis and apoptosis-related proteins were detected in each group. For in vivo treatments, periodontitis was ligature-induced in the first molars of the bilateral maxilla in 12 Sprague Dawley (SD) rats. After six weeks, the ligatures were removed and all the induced molars underwent scaling and root planning (SRP). Then, the rats were divided into three groups according to the following treatments: SRP, saline solution; MB, phenothiazinium dye; and MB-PDT, MB and laser irradiation. Apoptotic macrophages, inflammation levels, and alveolar bone resorption in the periodontal tissues of rats were analyzed in each group. Results. In vitro, flow cytometry analysis demonstrated that 10 μM MB and 40 J/cm2 laser irradiation maximized the apoptosis rate (34.74%) in macrophages. Fluorescence probe and Western blot analyses showed that MB-PDT induced macrophage apoptosis via reactive oxygen species (ROS) and the mitochondrial-dependent apoptotic pathway. Conversely, the addition of exogenous antioxidant glutathione (GSH) and the pan-caspase inhibitor Z-VAD-FMK markedly reduced the apoptotic response in macrophages. In vivo, immunohistochemistry, histology, radiographic, and molecular biology experiments revealed fewer infiltrated macrophages, less bone loss, and lower IL-1β and TNF-α levels in the MB-PDT group than in the SRP and MB groups (P<0.05). Immunohistochemistry analysis also detected apoptotic macrophages in the MB-PDT group. Conclusion. MB-PDT could induce macrophage apoptosis in vitro and in rats with periodontitis. This may be another way for MB-PDT to relieve periodontitis in addition to its antimicrobial effect. Meanwhile, MB-PDT induced apoptosis in THP-1 macrophages via the mitochondrial caspase pathway.

scholarly journals Antimicrobial photodynamic therapy fighting polymicrobial infections – a journey from in vitro to in vivo

2020 ◽  
Vol 19 (10) ◽  
pp. 1332-1343
Author(s):  
Lisa Karner ◽  
Susanne Drechsler ◽  
Magdalena Metzger ◽  
Ara Hacobian ◽  
Barbara Schädl ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Bacterial Suspension ◽  
Antimicrobial Photodynamic Therapy ◽  
Led Light ◽  
Wound Model ◽  
Red Led ◽  
Polymicrobial Infections

The batericidal effects of antimicrobial photodynamic therapy (aPDT), using methylene blue as a photosensitizer and pulsed red LED light for activation, were tested in various environments in vitro and in a wound model in mice infected with a fecal bacterial suspension.

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