scholarly journals An osmium-peroxo complex for photoactive therapy of hypoxic tumors

2021 ◽  
Author(s):  
Nong Lu ◽  
Zhihong Deng ◽  
Jing Gao ◽  
Chao Liang ◽  
Haiping Xia ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Glutathione Peroxidase ◽  
Photocatalytic Oxidation ◽  
Lipid Peroxide ◽  
Light Irradiation ◽  
Peroxo Complex ◽  
Chemotherapeutic Drug ◽  
Practical Application ◽  
New Strategy

Abstract Its limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy (PDT). Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but upon light irradiation, can release a peroxo ligand O2•−, and is transformed into a cytotoxic osmium complex (Os1). The osmium-peroxo complex Os2 produces O2•− under light irradiation even in the absence of oxygen, and retains its phototoxicity in hypoxic tumors. Os1 is cytotoxic in the presence or absence of irradiation, behaves as a chemotherapeutic drug. The light-activated Os2 induces distinct ferroptosis, which is mediated by GSH degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4 (GPX4). In addition, Os2 causes photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) in living cancer cells, leading to ferroptosis. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A new strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

The effects of photodynamic therapy with Photodithazine on HPV 16 E6/E7 associated cervical cancer model

2011 ◽  
Vol 15 (03) ◽  
pp. 174-180 ◽  
Author(s):  
Lan Ying Wen ◽  
Su-Mi Bae ◽  
Jin Hwan Do ◽  
Kye-Shin Park ◽  
Woong Shick Ahn
Keyword(s):  
Cervical Cancer ◽  
Photodynamic Therapy ◽  
Growth Inhibition ◽  
Biological Significance ◽  
Light Irradiation ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Hpv 16

Photodynamic therapy (PDT) is a promising treatment for cancer that has been recently accepted in the clinic. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Photodithazine, on cervical cancer model. When human papillomavirus type 16 (HPV16)- transformed mouse TC-1 cells were exposed to varied doses of Photodithazine with light irradiation (6.25 J/cm2), the significant growth inhibition of TC-1 cells was observed at 0.75 μg/mL of Photodithazine. The damaged cells by Photodithazine/PDT were categorized to be early and late apoptosis, as determined by annexin V staining. Photodithazine was primarily localized at lysosome apparatus within TC-1 cells while it was rapidly accumulated and sustained for initial 3 h in tumor tissue of TC-1 tumor bearing mice after IV injection. The tumor growth inhibition by Photodithazine/PDT with light irradiation (300 J/cm2) was examined after injection of various concentration of Photodithazine in tumor mice system. Our results show that Photodithazine/PDT might have significant advantages in the selective killing of tumor lesions in HPV 16 E6/E7 associated cervical cancer model, both in vitro and in vivo.

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 In vivo 808 nm image-guided photodynamic therapy based on an upconversion theranostic nanoplatform

Nanoscale ◽  
2015 ◽  
Vol 7 (36) ◽  
pp. 14914-14923 ◽  
Author(s):  
Xiaomin Liu ◽  
Ivo Que ◽  
Xianggui Kong ◽  
Youlin Zhang ◽  
Langping Tu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Ligand Exchange ◽  
Image Guided ◽  
New Strategy

A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer.

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 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 KillerRed protein based in vivo photodynamic therapy and corresponding tumor metabolic imaging

2016 ◽  
Vol 09 (01) ◽  
pp. 1640001 ◽  
Author(s):  
Qiaoya Lin ◽  
Shuang Sha ◽  
Fei Yang ◽  
Honglin Jin ◽  
Zhihong Zhang
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Fluorescent Protein ◽  
Tumor Therapy ◽  
Light Irradiation ◽  
Metabolic Imaging ◽  
Metabolic States ◽  
Low Toxicity

Photodynamic therapy (PDT) gains wide attention as a useful therapeutic method for cancer. It is mediated by the oxygen and photosensitizer under the specific light irradiation to produce the reactive oxygen species (ROS), which induce cellular toxicity and regulate the redox potential in tumor cells. Nowadays, genetic photosensitizers of low toxicity and easy production are required to be developed. KillerRed, a unique red fluorescent protein exhibiting excellent phototoxic properties, has the potential to act as a photosensitizer in the application of tumor PDT. Meantime, the course of tumor redox metabolism during this treatment was rarely investigated so far. Thus here, we investigated the effects of KillerRed-based PDT on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of nicotinamide adenine dinucleotide hydrogen (NADH) and flavoprotein (Fp), two important metabolic coenzymes of tumor cells. Results showed the tumor growth had been significantly inhibited by KillerRed-based PDT treatment compared to control groups. A home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The Fp signal was elevated by nearly 4.5-fold, while the NADH signal decreased by 66% after light irradiation, indicating that Fp and NADH were oxidized in the course of KillerRed-based PDT. Furthermore, we also observed correlation between the fluorescence distribution of KillerRed and NADH. It suggests that the KillerRed protein based PDT might provide a new approach for tumor therapy accompanied by altering tumor metabolism.

scholarly journals Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy

2021 ◽  
Vol 11 (2) ◽  
pp. 136
Author(s):  
Shanghui Gao ◽  
Rayhanul Islam ◽  
Jun Fang
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Tumor Model ◽  
Micelle Formation ◽  
Light Irradiation ◽  
Zinc Protoporphyrin ◽  
Tumor Environment

Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an ester bond (HA-es-ZnPP), and we examined its anticancer PDT effect both in vitro and in vivo. HA-es-ZnPP exhibits high water-solubility and forms micelles of ~40 nm in aqueous solutions. HA-es-ZnPP shows fluorescence quenching without apparent 1O2 generation under light irradiation because of micelle formation. However, 1O2 was extensively generated when the micelle is disrupted, and ZnPP is released. Compared to native ZnPP, HA-es-ZnPP showed lower but comparable intracellular uptake and cytotoxicity in cultured mouse C26 colon cancer cells; more importantly, light irradiation resulted in 10-time increased cytotoxicity, which is the PDT effect. In a mouse sarcoma S180 solid tumor model, HA-es-ZnPP as polymeric micelles exhibited a prolonged systemic circulation time and the consequent tumor-selective accumulation based on the enhanced permeability and retention (EPR) effect was evidenced. Consequently, a remarkable anticancer PDT effect was achieved using HA-es-ZnPP and a xenon light source, without apparent side effects. These findings suggest the potential of HA-es-ZnPP as a candidate anticancer nanomedicine for PDT.

Effects of Vitamin E Administration on Platelet Function and Serum Lipid Peroxides in DOCA-Salt Hypertensive Rats

1991 ◽  
Vol 65 (04) ◽  
pp. 411-414 ◽  
Author(s):  
Keizo Umegaki ◽  
Hiromi Saegusa ◽  
Masato Kurokawa ◽  
Tomio Ichikawa
Keyword(s):  
Vitamin E ◽  
Platelet Function ◽  
Serum Lipid ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Hypertensive Rats ◽  
Serotonin Content ◽  
Serum Lipid Peroxide ◽  
Salt Hypertension

SummaryEffects of vitamin E on platelet function and serum lipid peroxide levels were investigated in DOCA-salt hypertensive rats. In the hypertensive rats, ADP- and collagen-induced platelet aggregation in whole blood were markedly attenuated and accompanied by a reduction of serotonin content as compared with the normotensive controls. These facts indicated the appearance of exhausted platelets, which have already been activated in vivo, due to the hypertension. Platelet vitamin E levels were decreased by 50%, while serum lipid peroxide levels were increased 3.6-fold in the hypertensive rats. Vitamin E administration (10 times the dietary intake) during the experimental periods did not influence either the aggregability or the serotonin content of platelets from the hypertensive rats. However, vitamin E administration significantly prevented the elevation of serum tipid peroxides due to the hypertension. These results suggest that vitamin E administration has little effect on platelet activation in vivo due to DOCA-salt hypertension.

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