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Photosensitizer-Conjugated Human Serum Albumin Nanoparticles for Effective Photodynamic Therapy  [cached]
Hayoung Jeong, MyungSook Huh, So Jin Lee, Heebeom Koo, Ick Chan Kwon, Seo Young Jeong, Kwangmeyung Kim
Theranostics , 2011,
Abstract: Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. The focus of this study was the development of tumor-targeting albumin nanoparticles containing photosensitizers for efficient PDT. To produce tumor-targeting albumin nanoparticles, the hydrophobic photosensitizer, chlorin e6 (Ce6), was chemically conjugated to human serum albumin (HSA). The conjugates formed self-assembled nanoparticle structures with an average diameter of 88 nm under aqueous conditions. As expected, the Ce6-conjugated HSA nanoparticles (Ce6-HSA-NPs) were nontoxic in their native state, but upon illumination with the appropriate wavelength of light, they produced singlet oxygen and damaged target tumor cells in a cell culture system. Importantly, when the nanoparticles were injected through the tail vein into tumor-bearing HT-29 mice, Ce6-HSA-NPs compared with free Ce6 revealed enhanced tumor-specific biodistribution and successful therapeutic results following laser irradiation. These results suggest that highly tumor-specific albumin nanoparticles have the potential to serve not only as efficient therapeutic agents, but also as photodynamic imaging (PDI) reagents in cancer treatment.
Porphyrins : Dynamic Photosensitizer in Photodynamic Therapy  [cached]
Mr. L. Jayashankar,Dr. R. Vijayaraghavan
Pharmaceutical Reviews , 2007,
Abstract: Photosensitizer : A drug or chemical compound used in photodynamic therapy (treating cancer). When absorbed by cancer cells and exposed to light of specific wavelengths, the drug becomes active and kills the cancer cells 1,2 .Photodynamic therapyPhoto-therapy is the term used to describe treatments which use light to achieve their effects. Examples include the treatment of seasonal affective disorder (SAD) in winter by the controlled use of artificial light, and blue light exposure which is used to treat new-born babies with neonatal jaundice. In the case of the latter, blue light reacts with bilirubin, the yellow pigment responsible for producing the skin discolouration, and turns it into a more soluble form which is easier to excrete from the body.
Intracellular ZnO Nanorods Conjugated with Protoporphyrin for Local Mediated Photochemistry and Efficient Treatment of Single Cancer Cell
Kishwar S,Asif MH,Nur O,Willander M
Nanoscale Research Letters , 2010,
Abstract: ZnO nanorods (NRs) with high surface area to volume ratio and biocompatibility is used as an efficient photosensitizer carrier system and at the same time providing intrinsic white light needed to achieve cancer cell necrosis. In this letter, ZnO nanorods used for the treatment of breast cancer cell (T47D) are presented. To adjust the sample for intracellular experiments, we have grown the ZnO nanorods on the tip of borosilicate glass capillaries (0.5 μm diameter) by aqueous chemical growth technique. The grown ZnO nanorods were conjugated using protoporphyrin dimethyl ester (PPDME), which absorbs the light emitted by the ZnO nanorods. Mechanism of cytotoxicity appears to involve the generation of singlet oxygen inside the cell. The novel findings of cell-localized toxicity indicate a potential application of PPDME-conjugated ZnO NRs in the necrosis of breast cancer cell within few minutes.
CdTe Quantum Dot/Dye Hybrid System as Photosensitizer for Photodynamic Therapy  [cached]
Rakovich Aliaksandra,Savateeva Diana,Rakovich Tatsiana,Donegan John
Nanoscale Research Letters , 2010,
Abstract: We have studied the photodynamic properties of novel CdTe quantum dots—methylene blue hybrid photosensitizer. Absorption spectroscopy, photoluminescence spectroscopy, and fluorescence lifetime imaging of this system reveal efficient charge transfer between nanocrystals and the methylene blue dye. Near-infrared photoluminescence measurements provide evidence for an increased efficiency of singlet oxygen production by the methylene blue dye. In vitro studies on the growth of HepG2 and HeLa cancerous cells were also performed, they point toward an improvement in the cell kill efficiency for the methylene blue-semiconductor nanocrystals hybrid system.
Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy  [cached]
Peng Huang, Cheng Xu, Jing Lin, Can Wang, Xiansong Wang, Chunlei Zhang, Xuejiao Zhou, Shouwu Guo, Daxiang Cui
Theranostics , 2011,
Abstract: Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT.
Development of Polymeric Cargo for Delivery of Photosensitizer in Photodynamic Therapy
Byoung-chan Bae,Kun Na
International Journal of Photoenergy , 2012, DOI: 10.1155/2012/431975
Abstract: Photodynamic therapy (PDT), which employs photosensitizers (PSs), a light source with appropriate wavelength, and oxygen molecules, has potential for the treatment of various tumors and nononcological diseases due to its high efficiency in directly producing cellular death, vascular shutdown, and immune activation. After the clinical success of Photofrin (porphyrin derivative), many PSs were developed with improved optical and chemical properties. However, some weak points such as low solubility and nonspecific phototoxicity induced by hydrophobic PSs still remain. In order to overcome these problems, various polymeric carriers for PS delivery have been intensively developed. Here, we report recent approaches to the development of polymeric carriers for PS delivery and discuss the physiological advantages of using polymeric carriers in PDT. Therefore, this paper provides helpful information for the design of new PSs without the weaknesses of conventional ones.
Assessment of DNA Damage after Photodynamic Therapy Using a Metallophthalocyanine Photosensitizer
A. El-Hussein,M. Harith,H. Abrahamse
International Journal of Photoenergy , 2012, DOI: 10.1155/2012/281068
Abstract: Photodynamic therapy (PDT) is a chemotherapeutic approach that utilizes a bifunctional reagent, a photosensitizer (PS) that localizes to the target tissue relative to the surrounding tissue and is toxic when exposed to laser light. PDT rapidly induces cell death, inflammatory and immune reactions, and damage of the microvasculature. DNA damage results from a variety of factors including UV-light, X-rays, ionizing radiation, toxins, chemicals, or reactive oxygen species. The aim of this study was to determine the effect of PDT as well as the influence of presensitization leading to the adaptive response (AR) on the integrity of DNA. Lung (A549), breast (MCF-7), and esophageal (SNO) cancer cells and Zn sulfophthalocyanine as PS with irradiation conditions of 10 J/cm2 at 636 nm were used. Subcellular localization of PS, cell morphology, and viability after PDT and DNA damage were determined. A significant decrease in viability and marked DNA damage was observed in all 3 cancer cell types in response to PDT while the adaptive response was demonstrated to significantly decrease the effectiveness of the PDT.
Efficient Photodynamic Therapy against Gram-Positive and Gram-Negative Bacteria Using THPTS, a Cationic Photosensitizer Excited by Infrared Wavelength  [PDF]
Stanislaw Schastak,Svitlana Ziganshyna,Burkhard Gitter,Peter Wiedemann,Thomas Claudepierre
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011674
Abstract: The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to kill antibiotic-resistant bacteria uses light in combination with a photosensitizer to induce a phototoxic reaction. Concentrations of 1, 10 and 100μM of tetrahydroporphyrin-tetratosylat (THPTS) and different incubation times (30, 90 and 180min) were used to measure photodynamic efficiency against two Gram-positive strains of S.aureus (MSSA and MRSA), and two Gram-negative strains of E.coli and P.aeruginosa. We found that phototoxicity of the drug is independent of the antibiotic resistance pattern when incubated in PBS for the investigated strains. Also, an incubation with 100μM THPTS followed by illumination, yielded a 6lg (≥99.999%) decrease in the viable numbers of all bacteria strains tested, indicating that the THPTS drug has a high degree of photodynamic inactivation. We then modulated incubation time, photosensitizer concentration and monitored the effect of serum on the THPTS activity. In doing so, we established the conditions to obtain the strongest bactericidal effect. Our results suggest that this new and highly pure synthetic compound should improve the efficiency of photodynamic therapy against multiresistant bacteria and has a significant potential for clinical applications in the treatment of nosocomial infections.
Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy  [cached]
Chen Zhi-Long,Sun Yun,Huang Peng,Yang Xiao-Xia
Nanoscale Research Letters , 2009,
Abstract: As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT) is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs) were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl) porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4) and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.
Singlet Oxygen in Antimicrobial Photodynamic Therapy: Photosensitizer-Dependent Production and Decay in E. coli  [PDF]
Xavier Ragàs,Xin He,Montserrat Agut,Mónica Roxo-Rosa,António Rocha Gonsalves,Arménio C. Serra,Santi Nonell
Molecules , 2013, DOI: 10.3390/molecules18032712
Abstract: Several families of photosensitizers are currently being scrutinized for antimicrobial photodynamic therapy applications. Differences in physical and photochemical properties can lead to different localization patterns as well as differences in singlet oxygen production and decay when the photosensitizers are taken up by bacterial cells. We have examined the production and fate of singlet oxygen in Escherichia coli upon photosensitization with three structurally-different cationic photosensitizers, namely New Methylene Blue N (NMB), a member of the phenothiazine family, ACS268, a hydrophobic porphyrin with a single cationic alkyl chain, and zinc(II)-tetramethyltetrapyridinoporphyrazinium salt, a phthalocyanine-like photosensitizer with four positive charges on the macrocycle core. The kinetics of singlet oxygen production and decay indicate different localization for the three photosensitizers, whereby NMB appears to localize in an aqueous-like microenvironment, whereas ACS268 localizes in an oxygen-shielded site, highly reactive towards singlet oxygen. The tetracationic zinc(II) tetrapyridinoporphyrazine is extensively aggregated in the bacteria and fails to produce any detectable singlet oxygen.
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