Search results for: photodynamic therapy

Authors: E.A. Kuchma

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Photodynamic therapy (PDT) is considered an alternative and minimally invasive cancer treatment modality compared to chemotherapy and radiation therapy. PDT includes three main components: a photosensitizer (PS), oxygen, and a light source. PS is injected into the patient's body and then selectively accumulates in the tumor. However, the light used in PDT (spectral range 400–700 nm) is limited to superficial lesions, and the light penetration depth does not exceed a few cm. The problem of PDT (poor visible light transmission) can be solved by using X-rays. The penetration depth of X-rays is ten times greater than that of visible light. Therefore, X-ray radiation easily penetrates through the tissues of the body. The aim of this work is to develop universal nanocomposites for X-ray photodynamic therapy of deep and superficial tumors using scintillation nanoparticles of gadolinium fluoride (GdF3), doped with Tb3+, coated with a biocompatible coating (PEG) and photosensitizer RB (Rose Bengal). PEG@GdF3:Tb3+(15%) – RB could be used as an effective X-ray, UV, and photoluminescent mediator to excite a photosensitizer for generating reactive oxygen species (ROS) to kill tumor cells via photodynamic therapy. GdF3 nanoparticles can also be used as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI).

Keywords: X-ray induced photodynamic therapy, scintillating nanoparticle, radiosensitizer, photosensitizer

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Authors: Kave Moloudi, Heidi Abrahamse, Blassan P. George

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Radiotherapy (RT) and photodynamic therapy (PDT) are both forms of cancer treatment that aim to kill cancer cells while minimizing damage to healthy tissue. The similarity between RT and PDT lies in their mechanism of action. Both treatments use energy to damage cancer cells. RT uses high-energy radiation to damage the DNA of cancer cells, while PDT uses light energy to activate a photosensitizing agent, which produces reactive oxygen species (ROS) that damage the cancer cells. Both treatments require careful planning and monitoring to ensure the correct dose is delivered to the tumor while minimizing damage to surrounding healthy tissue. They are also often used in combination with other treatments, such as surgery or chemotherapy, to improve overall outcomes. However, there are also significant differences between RT and PDT. For example, RT is a non-invasive treatment that can be delivered externally or internally, while PDT requires the injection of a photosensitizing agent and the use of a specialized light source to activate it. Additionally, the side effects and risks associated with each treatment can vary. In this review, we focus on generalizing the 6Rs of radiobiology in PDT, which can open a window for the clinical application of Radio-photodynamic therapy with minimum side effects. Furthermore, this review can open new insight to work on and design new radio-photosensitizer agents in Radio-photodynamic therapy.

Keywords: radiobiology, photodynamic therapy, radiotherapy, 6Rs in radiobiology, ROS, DNA damages, cellular and molecular mechanism, clinical application.

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Authors: Syue-Liang Lin, C. Allen Chang

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Luminescence imaging is an important technique used in biomedical research and clinical diagnostic applications in recent years. Concurrently, the development of NIR luminescence probes / imaging contrast agents has helped the understanding of the structural and functional properties of cells and animals. Photodynamic therapy (PDT) is used clinically to treat a wide range of medical conditions, but the therapeutic efficacy of general PDT for deeper tumor was limited by the penetration of excitation source. The tumor targeting biomedical nanomaterials UCNP@PS (upconversion nanoparticle conjugated with photosensitizer) for photodynamic therapy and near-infrared imaging of cancer will be developed in our study. Synthesis and characterization of biomedical nanomaterials were completed in this studies. The spectrum of UCNP was characterized by photoluminescence spectroscopy and the morphology was characterized by Transmission Electron Microscope (TEM). TEM and XRD analyses indicated that these nanoparticles are about 20~50 nm with hexagonal phase. NaYF₄:Ln³⁺ (Ln= Yb, Nd, Er) upconversion nanoparticles (UCNPs) with core / shell structure, synthesized by thermal decomposition method in 300°C, have the ability to emit visible light (upconversion: 540 nm, 660 nm) and near-infrared with longer wavelength (downconversion: NIR: 980 nm, 1525 nm) by absorbing 800 nm NIR laser. The information obtained from these studies would be very useful for applications of these nanomaterials for bio-luminescence imaging and photodynamic therapy of deep tumor tissue in the future.

Keywords: Near Infrared (NIR), lanthanide, core-shell structure, upconversion, theranostics

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Authors: Prabhavathi Sundaram, Heidi Abrahamse

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In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

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Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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Authors: Yong Zhang

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Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

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Authors: Bokolombe Pitchou Ngoy, John Mack, Tebello Nyokong

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Synthesis and photochemical studies of BODIPY dyes have been investigated in this work in order to have a broad benchmark of this functionalized photosensitizer for biological applications such as photodynamic therapy or antimicrobial activity. The common acid catalyzed synthetic method was used, and BODIPY dyes were obtained in quite a good yield (25 %) followed by bromination and Knoevenagel condensation to afford the BODIPY dyes conjugated with maximum absorbance in the near-infrared region of the electromagnetic spectrum. The fluorescence lifetimes, fluorescence quantum yield, and Singlet oxygen quantum yield of the conjugated BODIPY dyes were determined in different solvents by using Time Correlation Single Photon Counting (TCSPC), fluorimeter, and Laser Flash Photolysis respectively. It was clearly shown that the singlet oxygen quantum yield was higher in THF followed by DMSO compared to another solvent. The same trend was observed for the fluorescence lifetimes.

Keywords: BODIPY, photodynamic therapy, photosensitizer, singlet oxygen

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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Authors: Rina Lee, Chung-Hun Oh, Eunjin Lee, Jeongyun Kim

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The Photodynamic therapy (PDT) is a treatment that uses a photosensitizer as a drug to damage and kill cancer cells. After injecting the photosensitizer into the bloodstream, the drug is absorbed by cancer cells selectively. Then the area to be treated is exposed to specific wavelengths of light and the photosensitizer produces a form of oxygen that kills nearby cancer cells. PDT is has an advantage to destroy the tumor with minimized side-effects on normal cells. But, PDT is not a completed method for cancer therapy. Because the mechanism of PDT is quite clear yet and the parameters such as intensity of light and dose of photosensitizer are not optimized for different types of cancers. To optimize these parameters, we suggest a novel microfluidic system to automatically control intensity of light exposure with a personal computer (PC). A polydimethylsiloxane (PDMS) microfluidic chip is composed with (1) a cell culture channels layer where cancer cells were trapped to be tested with various dosed photofrin (1μg/ml used for the test) as the photosensitizer and (2) a color dye layer as a neutral density (ND) filter to reduce intensity of light which exposes the cell culture channels filled with cancer cells. Eight different intensity of light (10%, 20%, …, 100%) are generated through various concentrations of blue dye filling the ND filter. As a light source, a light emitting diode (LED) with 635nm wavelength was placed above the developed PDMS microfluidic chip. The total time for light exposure was 30 minutes and HeLa and PC3 cell lines of cancer cells were tested. The cell viability of cells was evaluated with a Live/Dead assay kit (L-3224, Invitrogen, USA). The stronger intensity of light exposed, the lower viability of the cell was observed, and vice versa. Therefore, this system was demonstrated through investigating the PDT against cancer cell to optimize the parameters as critical light intensity and dose of photosensitizer. Our results suggest that the system can be used for optimizing the combinational parameters of light intensity and photosensitizer dose against diverse cancer cell types.

Keywords: photodynamic therapy, photofrin, high throughput screening, hela

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Authors: Hadeel Seraj, Mohammed Khoshhal, Mustafa Alhamoud, Hassan Alhashim, Anas Alsaif, Amro Abukhashabah

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Central serous chorioretinopathy (CSCR) is an idiopathic retinal disease characterized by localized serous detachment of the neurosensory retina at the macula. To date, there is no high-quality evidence of recent updates on treating acute CSCR, focusing on photodynamic therapy (PDT) and anti-vascular endothelial growth factor (anti-VEGF). Hence, this review aims to systematically review the latest treatment strategies for acute CSCR. Methodology: The following electronic databases were used for a comprehensive and systematic literature review: MEDLINE, EMBASE, and Cochrane. In addition, we analyzed studies comparing PDT with placebo, anti-VEGF with placebo, or PDT with anti-VEGF in treating acute CSC eyes with no previous intervention. Results: Seven studies were included, with a total of 292 eyes. The overall positive results were significantly higher among patients who received PDT compared to control groups (OR = 7.96, 95% CI, 3.02 to 20.95, p < 0.001). The proportions of positive results were 81.0% and 97.1% among patients who received anti-VEGF and PDT, respectively, with no statistically significant differences between the groups. In addition, there were no significant differences between anti-VEGF and control groups. In contrast, PDT was significantly associated with lower recurrence odds than the control groups (OR = 0.12, 95% CI, 0.04 to 0.39, p = 0.042). Conclusion: According to our findings, PDT showed higher positive results than Anti-VEGF in acute CSCR. In addition, PDT was significantly associated with a lower recurrence rate than the control group. However, the analysis needs to be confirmed and updated by large-scale, well-designed RCTs.

Keywords: central serous chorioretinopathy, Acute CSCR, photodynamic therapy, anti-vascular endothelial growth factor

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Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

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In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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Authors: Mahnoor Khan, Bashir Ahmad, Khizar Hayat, Saad Ahmad Khan, Laiba Ahmad, Shumaila Bashir, Abid Ali Khan

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The objective of this study was to synthesize the smallest possible size of ZnO NPs using a modified wet chemical synthesis method and to prepare core shell using polyethylene glycol (PEG) as shell material. Advanced and sophisticated techniques were used to confirm the synthesis, size, and shape of these NPs. Rounded, clustered NPs of size 5.343 nm were formed. Both the plain and core shell NPs were tested against MDR bacteria (E. cloacae, E. amnigenus, Shigella, S. odorifacae, Citrobacter, and E. coli). Both of the NPs showed excellent antibacterial properties, whereas E. cloacae showed maximum zone of inhibition of 16 mm, 27 mm, and 32 mm for 500 μg/ml, 1000 μg/ml, and 1500 μg/ml, respectively for plain ZnO NPs and 18 mm, 28 mm and 35 mm for 500 μg/ml, 1000 μg/ml and 1500 μg/ml for core shell NPs. These NPs were also biocompatible on human red blood cells showing little hemolysis of only 4% for 70 μg/ml for plain NPs and 1.5% for 70 μg/ml for core shell NPs. Core shell NPs were highly biocompatible because of the PEG. Their therapeutic effect as photosensitizers in photodynamic therapy (PDT) for cancer treatment was also monitored. The cytotoxicity of ZnO and PEG-ZnO was evaluated using MTT assay. Our results demonstrated that these NPs could generate ROS inside tumor cells after irradiation which in turn initiates an apoptotic pathway leading to cell death hence proving to be an effective candidate for PDT.

Keywords: ZnO, hemolysis, cytotoxiciy assay, photodynamic therapy, antibacterial

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Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Louisa Han Lin Tan, Poh Sim Kang, Wei Ming Loi, Susan Jane Rickard Liow

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The efficacy of music for improving speech and language has been shown across ages and diagnoses. Across the world, the wide range of therapy settings and increasing number of children diagnosed with special needs demand more cost and time effective service delivery. However, research exploring co-treatment models on children other than those with Autism Spectrum Disorder remains sparse. The aim of this research was to determine the efficacy of music for improving language in children with special needs, and generalizability of therapy effects. 25 children (7 to 12 years) were split into three groups – A, B and control. A cross-over design with direct therapy (storytelling) with or without music, and indirect therapy was applied with two therapy phases lasting 6 sessions each. Therapy targeted three prepositions in each phase. Baseline language abilities were assessed, with re-assessment after each phase. The introduction of music in therapy led to significantly greater improvement (p=.046, r=.53) in associated language abilities, with case studies showing greater effectiveness in developmentally appropriate target prepositions. However, improvements were not maintained once direct therapy ceased. As such, the incorporation of music could lead to greater efficiency and effectiveness of language therapy in children with special needs, but sustainability and generalizability of therapy effects both require further exploration.

Keywords: music, language therapy, children, special needs

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Authors: Mohamed Sharof Mostafa, Atefeh Ahmadi

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Most of traditional single modality psychotherapy and counselling approaches to clients’ problems are based on the application of one therapy in all sessions. Modern developments in these sciences focus on eclectic and integrative interventions to consider all dimensions of an issue and all characteristics of the clients. This paper presents and overview eclectic therapy and its pros and cons. In addition, multiple intelligence theory and its application in eclectic therapy approaches are mentioned.

Keywords: eclectic therapy, client, multiple intelligence theory, dimensions

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Authors: Auj-E Taqaddas

Abstract:

The use of proton beam therapy is increasing globally. It seems to offer dosimetric advantages, especially in paediatric central nervous system (CNS) and brain tumours. A short E-survey was conducted to assess the clinical, technical, and educational resources and strategies employed in the state of the art proton beam therapy (PBT) centres in the USA to determine the current status of proton beam therapy. The study also aimed at finding out which PBT skills are in demand as well as what improvements are needed to ensure efficient treatment planning, delivery, and dosimetry. The study resulted in identifying areas for future research and development and in identifying cancers for which PBT is most suitable compared to other modalities to facilitate the implementation and use of PBT in clinical settings for cancer treatment.

Keywords: cancer, intensity modulated proton therapy, proton beam therapy, single field uniform scanning

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Authors: Siamak Samani, Nadereh Sohrabi

Abstract:

Psychological nano-therapy is a new method based on systems theory. According to the theory, systems with severe dysfunctions are resistant to changes. Psychological nano-therapy helps the therapists to break this ice. Two key concepts in psychological nano-therapy are nano-functions and nano-behaviors. The most important step in psychological nano-therapy in family therapy is selecting the most effective nano-function and nano-behavior. The aim of this study was to check the effectiveness of psychological nano-therapy for family therapy. One group pre-test-post-test design (quasi-experimental Design) was applied for research. The sample consisted of ten families with severe marital conflict. The important character of these families was resistance for participating in family therapy. In this study, sending respectful (nano-function) text massages (nano-behavior) with cell phone were applied as a treatment. Cohesion/respect sub scale from self-report family processes scale and family readiness for therapy scale were used to assess all family members in pre-test and post-test. In this study, one of family members was asked to send a respectful text massage to other family members every day for a week. The content of the text massages were selected and checked by therapist. To compare the scores of families in pre-test and post-test paired sample t-test was used. The results of the test showed significant differences in both cohesion/respect score and family readiness for therapy between per-test and post-test. The results revealed that these families have found a better atmosphere for participation in a complete family therapy program. Indeed, this study showed that psychological nano-therapy is an effective method to make family readiness for therapy.

Keywords: family therapy, family conflicts, nano-therapy, family readiness

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Authors: Farnaz Dehkhoda

Abstract:

This study was conducted to compare the effectiveness of active and receptive music-therapy on anxiety in cancer patients undergoing chemotherapy or radiotherapy. 184 young adult patients, who were diagnosed with early stage cancer and were undergoing treatment, were divided into three groups. Two groups received music therapy as a parallel treatment and the third group was control group. In active music-therapy, a music specialist helped the patients to play guitar and sing. In the receptive music-therapy, patients preferred pre-recorded music played by MP3 player. The level of anxiety was measured by the Beck Anxiety Inventory as pre-test and post-test. ANCOVA revealed that both types of music-therapy reduced anxiety level of patients and the active music-therapy intervention found to be more effective. The results suggest that music-therapy can be applied as an intervention method contemporary with cancer medical treatment, for improving quality of life in cancer patients by reducing their anxiety.

Keywords: Anxiety, Cancer, Chemotherapy, Music-therapy

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Authors: Sachinkumar Patil, Sonali Patil, Shitalkumar Patil

Abstract:

Nanoparticles played important role in the biomedicine. New advanced methods having great potential apllication in the diagnosis and therapy of cancer. Now a day’s magnetic nanoparticles used in cancer therapy. Cancer is the major disease causes death. Magnetic nanoparticles show response to the magnetic field on the basis of this property they are used in cancer therapy. Cancer treated with hyperthermia by using magnetic nanoparticles it is unconventional but more safe and effective method. Magnetic nanoparticles prepared by using different innovative techniques that makes particles in uniform size and desired effect. Magnetic nanoparticles already used as contrast media in magnetic resonance imaging. A magnetic nanoparticle has been great potential application in cancer diagnosis and treatment as well as in gene therapy. In this review we will discuss the progress in cancer therapy based on magnetic nanoparticles, mainly including magnetic hyperthermia, synthesis and characterization of magnetic nanoparticles, mechanism of magnetic nanoparticles and application of magnetic nanoparticles.

Keywords: magnetic nanoparticles, synthesis, characterization, cancer therapy, hyperthermia, application

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Authors: Yu Chen

Abstract:

Auricular-magnet therapy is the development of auricular acupuncture. It is a powerful, convenient, and quick result-achieving therapeutic method. This therapy works by using magnetic discs to be placed on acupuncture points on the ears to treat diseases and improve health. In this study, the fundamental principles, indications, and contraindications of this therapy are discussed. Five examples, including reducing blood glucose levels, healing gangrene for diabetes patients, and treating Bell's palsy, are presented. Auricular-magnet therapy is a powerful development in acupuncture.

Keywords: auricular-magnet therapy, Bell’s palsy, diabetes mellitus, food craving, insomnia, nausea, obesity

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Authors: Bae Yu been, Choi Sung won, Lee Ju yeon, Yang Dan Bi

Abstract:

The purpose of this study is to develop a self-help therapy program for bipolar disorder (BD). Psychosocial treatment is adjunct to pharmacotherapy for BD, however, it is limited and they demand high costs. Therefore, the objective of the study is to overcome these limitations by developing the self-treatment for BD. The study was examined the efficacy of the self-treatment program for BD. A randomized controlled trial compared the self-help therapy (ST) intervention with a treatment as usual (TAU) group. ST group has conducted the program for 8 weeks (16 sessions). Mood chart, Quality of Life in Bipolar Disorder Questionnaire, Attitudes toward seeking professional help Scale, BIS, CERQ, YMRS, MADRS were used by pre, post, and follow up. The efficacy of the self-help therapy was analyzed by using mixed ANOVAs. There were significant differences in the rate of occurrence of mania or depression between the two groups. ST group reported stable moods on mood chart, and reductions in mood symptoms and improvements in quality of life and treatment adherence. This study was confirmed applicable to BD to the self-help therapy for patients with BD conducted first in Korea.

Keywords: self help therapy, bipolar disorder, self help, self therapy

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Authors: G. Fomo, O. J. Achadu, T. Nyokong

Abstract:

Nanoconjugates of graphene quantum dots (GQDs) and 4-(tetrakis-5-(trifluoromethyl)-2-mercaptopyridinephthalocyanine (H₂Pc(OPyF₃)₄) or 4-(tetrakis-5-(trifluoromethyl)-2-mercaptopyridinephthalocyaninato) zinc (II) (ZnPc(OPyF₃)₄) were synthesized via a novel in situ one-step route. The bottom-up approach for the prepared conjugates could ensure the intercalation of the phthalocyanines (Pcs) directly onto the edges or surface of the GQDs and or non-covalent coordination using the π-electron systems of both materials. The as-synthesized GQDs and their Pcs conjugates were characterized using different spectroscopic techniques and their photophysicochemical properties evaluated. The singlet oxygen quantum yields of the Pcs in the presence of GQDs were enhanced due to Förster resonance energy transfer (FRET) occurrence within the conjugated hybrids. Hence, these nanoconjugates are potential materials for photodynamic therapy (PDT) and photocatalysis applications.

Keywords: graphene quantum dots, metal free fluorinated phthalocyanine, zinc fluorinated phthalocyanine, photophysicochemical properties

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Authors: Ya-Hui Wang

Abstract:

Lower speech therapy rate of tracheostomized patient was noted in comparison with previous researches. This study is aim to shed light on the referral status of speech therapy in those patients in Taiwan. This study developed an analysis for the size and key characteristics of the population of tracheostomized in-patient in the Taiwan. Method: We analyzed National Healthcare Insurance data (The Collaboration Center of Health Information Application, CCHIA) from Jan 1 2010 to Dec 31 2010. Result: over ages 3, number of tracheostomized in-patient is directly proportional to age. A high service loading was observed in North region in comparison with other regions. Only 4.87% of the tracheostomized in-patients were referred for speech therapy, and 1.9% for swallow examination, 2.5% for communication evaluation.

Keywords: refer, speech therapy, training, rehabilitation

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Authors: Eman Tadros, Natasha Finney

Abstract:

The following case study involving a high-conflict, Children’s Services Bureau (CSB) referred couple is analyzed and reviewed through an integrated lens of structural family therapy and dialectical behavior therapy. In structural family therapy, normal family development is not characterized by a lack of problems, but instead by families’ having developed a functional structure for dealing with their problems. Whereas, in dialectical behavioral therapy normal family development can be characterized by having a supportive and validating environment, where all family members feel a sense of acceptance and validation for who they are and where they are in life. The clinical case conceptualization highlights the importance of conceptualizing how change occurs within a therapeutic setting. In the current case study, the couple did not only experience high-conflict, but there were also issues of substance use, health issues, and other complicating factors. Clinicians should view their clients holistically and tailor their treatment to fit their unique needs. In this framework, change occurs within the family unit, by accepting each member as they are, while at the same time working together to change maladaptive familial structures.

Keywords: couples, dialectical behavior therapy, high-conflict, structural family therapy

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Authors: M. Krishna

Abstract:

The study was intended to identify if scalp cooling therapy is effective on preventing chemotherapy-induced hair loss among cancer patients. Critical literature of non-randomized controlled trials was used to investigate whether scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. The review identified that scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. Most of the patients receiving chemotherapy experience alopecia. It is also perceived as the worst effect of chemotherapy. This may be severe and lead the patients to withdraw the chemo treatment. The image disturbance caused by alopecia will make the patient depressed and will lead to declined immunity. With the knowledge on effectiveness of scalp cooling therapy on preventing chemotherapy-induced alopecia, patient undergoing chemotherapy will not be hesitant to undergo the treatment. Patients are recommended to go through scalp cooling therapy every chemo cycle and the proper therapy duration is 30 minutes before, during chemo. The suggested duration of the scalp cooling therapy is 45-90 minutes for an effective and positive outcome. This finding is excluding other factors of alopecia such as menopause, therapeutic drugs, poor hair density, liver function problems, and drug regimes.

Keywords: alopecia, cancer, chemotherapy, scalp cooling therapy

Procedia PDF Downloads 178