scholarly journals A Comprehensive Tutorial onIn VitroCharacterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Tobias Kiesslich ◽  
Anita Gollmer ◽  
Tim Maisch ◽  
Mark Berneburg ◽  
Kristjan Plaetzer
Keyword(s):  
Photodynamic Therapy ◽  
Cell Biology ◽  
Wide Spectrum ◽  
Photophysical Properties ◽  
Intracellular Localization ◽  
Initial Step ◽  
Photodynamic Inactivation ◽  
Comprehensive Collection ◽  
Light Protection

In vitroresearch performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS) intended for application in photodynamic therapy (PDT) of cancer or photodynamic inactivation (PDI) of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performingin vitroexperiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research.

scholarly journals Recruitment and organization of ESCRT-0 and ubiquitinated cargo via condensation

2021 ◽  
Author(s):  
Sudeep Banjade ◽  
Lu Zhu ◽  
Jeffrey Jorgensen ◽  
Sho Suzuki ◽  
Scott D. Emr
Keyword(s):  
Membrane Proteins ◽  
Self Assembly ◽  
Cell Biology ◽  
Substrate Recognition ◽  
Initial Step ◽  
Binding Interactions ◽  
Vacuole Membrane ◽  
Multivalent Interactions ◽  
Cargo Sorting

AbstractThe general mechanisms by which ESCRTs are specifically recruited to various membranes, and how ESCRT subunits are spatially organized remain central questions in cell biology. At the endosome and lysosomes, ubiquitination of membrane proteins triggers ESCRT-mediated substrate recognition and degradation. Using the yeast lysosome/vacuole, we define the principles by which substrate engagement by ESCRTs occurs at this organelle. We find that multivalent interactions between ESCRT-0 and polyubiquitin is critical for substrate recognition at yeast vacuoles, with a lower-valency requirement for cargo engagement at endosomes. Direct recruitment of ESCRT-0 induces dynamic foci on the vacuole membrane, and forms fluid condensates in vitro with polyubiquitin. We propose that self-assembly of early ESCRTs induces condensation, an initial step in ESCRT-assembly/nucleation at membranes. This property can be tuned specifically at various organelles by modulating the number of binding interactions.One-Sentence SummaryCondensation of multivalent ESCRT-0/polyubiquitin assemblies organizes cargo sorting reactions at lysosomes

Mitochondria-targeted porphyrin-based photosensitizers containing triphenylphosphonium cations showing efficient in vitro photodynamic therapy effects

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1505-1514 ◽  
Author(s):  
Xing Guo ◽  
Hao Wu ◽  
Wei Miao ◽  
Yangchun Wu ◽  
Erhong Hao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Therapy ◽  
Fluorescence Spectroscopy ◽  
Hela Cells ◽  
Photophysical Properties ◽  
Quantum Yields ◽  
Subcellular Organelle

Subcellular organelle-targeted photosensitizers have recently reported to be effective photodynamic therapy (PDT) agents. In this work, three porphyrin-derived photosensitizers, containing one, two or four triphenylphosphonium targeting groups, were synthesized and characterized by NMR, HRMS, UV-vis and fluorescence spectroscopy. These photosensitizers showed similar photophysical properties to classical porphyrins and exhibited excellent [Formula: see text]O[Formula: see text] quantum yields in acetonitrile. Subcellular colocalization indicated that all three photosensitizers specifically stain the mitochondria of HeLa cells. Photosensitizer mito-dp, containing two triphenylphosphonium cations was found to be the most uptaken by cells and exhibited the best PDT effect with an effective phototoxicity (IC[Formula: see text] (light) [Formula: see text] 12.4 nM), suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.

Synthesis, photophysical properties and in vitro evaluation of a chlorambucil conjugated ruthenium(ii) complex for combined chemo-photodynamic therapy against HeLa cells

2017 ◽  
Vol 5 (24) ◽  
pp. 4623-4632 ◽  
Author(s):  
Jing-Xiang Zhang ◽  
Mei Pan ◽  
Cheng-Yong Su
Keyword(s):  
Photodynamic Therapy ◽  
Hela Cells ◽  
Photophysical Properties ◽  
Inhibitory Effect ◽  
Antiproliferative Effect ◽  
In Vitro Evaluation

We designed a new heteroleptic Ru(ii) complex CHL-RuL as an imaging-guided chemotherapy/PDT agent, which shows a moderate antiproliferative effect in dark and strong photodynamic inhibitory effect against HeLa cells.

Lysosome Targeting Bis-terpyridine Ruthenium(II) Complexes: Photophysical Properties and In Vitro Photodynamic Therapy

2020 ◽  
Vol 3 (9) ◽  
pp. 6025-6038
Author(s):  
Bingqing Liu ◽  
Yibo Gao ◽  
Mohammed A. Jabed ◽  
Svetlana Kilina ◽  
Guoquan Liu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Photophysical Properties

scholarly journals Curcumin derivatives as photosensitizers in photodynamic therapy: photophysical properties and in vitro studies with prostate cancer cells

2020 ◽  
Vol 19 (2) ◽  
pp. 193-206 ◽  
Author(s):  
K. T. Kazantzis ◽  
K. Koutsonikoli ◽  
B. Mavroidi ◽  
M. Zachariadis ◽  
P. Alexiou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Absorption Maximum ◽  
Photophysical Properties ◽  
In Vitro Studies ◽  
Prostate Cancer Cells ◽  
Curcumin Derivatives ◽  
Curcumin I

Increased absorption maximum for the dimethylaminocurcumin with strong PD effect on prostate cancer cells; Intense PD effect of curcumin III on prostate cancer cells; Exciting biphasic PD response by curcumin I and cinnamaldehyde-derived curcumin.

scholarly journals Farnesyl Diphosphate Synthase Is a Cytosolic Enzyme in Leishmania major Promastigotes and Its Overexpression Confers Resistance to Risedronate

2006 ◽  
Vol 5 (7) ◽  
pp. 1057-1064 ◽  
Author(s):  
Aurora Ortiz-Gómez ◽  
Carmen Jiménez ◽  
Antonio M. Estévez ◽  
Juana Carrero-Lérida ◽  
Luis M. Ruiz-Pérez ◽  
...  
Keyword(s):  
Drug Target ◽  
Leishmania Major ◽  
Intracellular Localization ◽  
Initial Step ◽  
Isoprenoid Biosynthesis ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Wild Type

ABSTRACT Farnesyl diphosphate synthase is the most likely molecular target of aminobisphosphonates (e.g., risedronate), a set of compounds that have been shown to have antiprotozoal activity both in vitro and in vivo. This protein, together with other enzymes involved in isoprenoid biosynthesis, is an attractive drug target, yet little is known about the compartmentalization of the biosynthetic pathway. Here we show the intracellular localization of the enzyme in wild-type Leishmania major promastigote cells and in transfectants overexpressing farnesyl diphosphate synthase by using purified antibodies generated towards a homogenous recombinant Leishmania major farnesyl diphosphate synthase protein. Indirect immunofluorescence, together with immunoelectron microscopy, indicated that the enzyme is mainly located in the cytoplasm of both wild-type cells and transfectants. Digitonin titration experiments also confirmed this observation. Hence, while the initial step of isoprenoid biosynthesis catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase is located in the mitochondrion, synthesis of farnesyl diphosphate by farnesyl diphosphate synthase is a cytosolic process. Leishmania major promastigote transfectants overexpressing farnesyl diphosphate synthase were highly resistant to risedronate, and the degree of resistance correlated with the increase in enzyme activity. Likewise, when resistance was induced by stepwise selection with the drug, the resulting resistant promastigotes exhibited increased levels of farnesyl diphosphate synthase. The overproduction of protein under different conditions of exposure to risedronate further supports the hypothesis that this enzyme is the main target of aminobisphosphonates in Leishmania cells.

Phthalocyanine-cRGD conjugate: synthesis, photophysical properties and in vitro biological activity for targeting photodynamic therapy

2016 ◽  
Vol 14 (10) ◽  
pp. 2985-2992 ◽  
Author(s):  
Liqiang Luan ◽  
Wenjuan Fang ◽  
Wei Liu ◽  
Minggang Tian ◽  
Yuxing Ni ◽  
...  
Keyword(s):  
Biological Activity ◽  
Photodynamic Therapy ◽  
Cross Section ◽  
Cellular Uptake ◽  
Photophysical Properties ◽  
Photon Absorption ◽  
Absorption Cross ◽  
Two Photon Absorption ◽  
Two Photon

Phthalocyanine-RGD conjugate was synthesized and examined for its two-photon absorption cross section (TPACS), cellular uptake, and photocytotoxicity.

scholarly journals Photophysical Properties of Pheophorbide-a Derivatives and Their Photodynamic Therapeutic Effects on a Tumor Cell LineIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kang-Kyun Wang ◽  
Jing Li ◽  
Bong-Jin Kim ◽  
Jeong-Hyun Lee ◽  
Hee-Won Shin ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Triplet State ◽  
Singlet Oxygen ◽  
Alkyl Group ◽  
Photophysical Properties ◽  
Hydroxyl Group ◽  
Quantum Yields ◽  
Therapeutic Effects ◽  
Pheophorbide A

Pheophorbide-a derivatives have been reported to be potential photosensitizers for photodynamic therapy (PDT). In this study, photophysics of pheophorbide-a derivatives (PaDs) were investigated along with their photodynamic tumoricidal effectin vitro. PaDs were modified by changing the coil length and/or making the hydroxyl group (–OH) substitutions. Their photophysical properties were studied by steady-state and time-resolved spectroscopic methods. The photodynamic tumoricidal effect was evaluated in the mouse breast cancer cell line (EMT6). Lifetime and quantum yield of fluorescence and quantum yields of triplet state and singlet oxygen were studied to determine the dynamic energy flow. The coil length of the substituted alkyl group did not significantly affect the spectroscopic properties. However, the substitution with the hydroxyl group increased the quantum yields of the triplet state and the singlet oxygen due to the enhanced intersystem crossing. In order to check the application possibility as a photodynamic therapy agent, the PaDs with hydroxyl group were studied for the cellular affinity and the photodynamic tumoricidal effect of EMT6. The results showed that the cellular affinity and the photodynamic tumoricidal effect of PaDs with the hydroxyl group depended on the coil-length of the substituted alkyl group.

scholarly journals Gene Therapeutic Approach for Inhibiting Hepatitis C Virus Replication Using a Recombinant Protein That Controls Interferon Expression

2010 ◽  
Vol 54 (12) ◽  
pp. 5048-5056 ◽  
Author(s):  
Chul Hyun Joo ◽  
Uk Lee ◽  
Young Ran Nam ◽  
Jae U. Jung ◽  
Heuiran Lee ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cultured Cells ◽  
Viral Vector ◽  
Wide Spectrum ◽  
Intracellular Localization ◽  
Treatment Modalities ◽  
In Cells

ABSTRACT The hepatitis C virus (HCV) is a continuing threat to public health. The systemic administration of interferon alpha with ribavirin is the only currently approved treatment. However, this treatment is associated with a wide spectrum of systemic side effects that limits its effectiveness; thus, there is an urgent need for new treatment modalities. In this study, we describe a novel anti-HCV strategy employing a recombinant transcription factor that we have engineered in such a way that NS3/4a viral protease controls its intracellular localization, thereby restoring interferon secretion specifically in cells infected with HCV. Proof-of-concept experiments validated the strategy, showing that the recombinant transcription factor was triggered to stimulate interferon promoter by NS3/4A and remained inactive in cells without NS3/4a. Using an adenovirus-associated viral vector delivery system, we found that the recombinant transcription factor inhibited HCV replication effectively in vitro in cultured cells.

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