<b>The Subcellular Localization of Zn(ll) Phthalocyanines and Their Redistribution on Exposure to Light</b>

Wood, Stephen C.; Holroyd, J. Andrew; Brown, Stanley B.

doi:10.1111/j.1751-1097.1997.tb08577.x

Cited by 119 publications

(64 citation statements)

References 9 publications

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“…47 Cationic pyridinium zinc phthalocyanine initially localizes in the lysosomes of RIF-1 cells, but on photoirradiation diffuses into the cytoplasm as well as selectively staining the nucleoli. 29,46 Anionic tetrasulfonated Zn(II) phthalocyanine and tetraglycine Zn(II) phthalocyanine have been shown to migrate from lysosomes mainly to the region of the nucleus after low-level light irradiation, whereas hydrophobic tetradioctylamine Zn(II) phthalocyanine, 46 tetra(m-hydroxyphenyl) chlorin and amphiphilic polyhematoporphyrin do not change their location. 29 The redistribution of PS from lysosomal compartments can be very rapid, taking minutes or even seconds, as found for polysubstituted Zn(II) phthalocyanines 46 and sulfonated aluminium phthalocyanines.…”

Section: Subcellular Redistribution Of Photosensitizers After Photoirmentioning

confidence: 99%

“…Pyridinium Zn(II) phthalocyanine and tetrasulfonated Zn(II) phthalocyanine, carrying four positive and four negative charges, respectively, appear to localize in lysosomes, whereas the neutral tetradiethanolamine Zn(II) phthalocyanine is diffusely localized through diverse intracellular membranes, with some preference for the Golgi complex. 46 …”

Section: Subcellular Distribution Of Photosensitizers In Vitromentioning

confidence: 99%

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Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency

Jans²,

2000

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IntroductionPhotodynamic therapy (PDT) is a relatively new cytotoxic treatment, predominantly used in anticancer approaches, that depends on the retention of photosensitizers (PS) in tumour cells and their activation within the tumour through irradiation with light of the appropriate wavelength. Photoactivated PS generate reactive oxygen species (singlet oxygen, 1 O 2 , and free radicals, such as ·OH, HO· 2 and ·O 2 -) which are able to damage cellular structures, meaning that PDT is particularly attractive as an alternative means to kill drug-and radioresistant tumour cells.1,2 Normal cells, however, are also able to accumulate PS and be damaged by them, so that prolonged skin photosensitization, light-sensitivity of the eye and other side-effects have proved to be severe limitations of PDT. When photoactivated, PS inflict damage on many types of biomolecules without any specificity, their action being mediated largely via the reactive oxygen species mentioned, none of which travel more than several tens of nanometers before reacting with a biomolecule. Keeping in mind that cell dimensions are of the order of micrometres or tens of micrometres, it is clear that the intracellular action of PS is restricted to the site of their subcellular location and the surrounding radius of not more than 40 nm.3-5 That uneven intracellular distribution of PS can lead to differences in toxicity has been shown using laser microbeam irradiation. 6In contrast to cell membranes and other cytoplasmic organelles, the cell nucleus 7-9 is known to be a very sensitive target for reactive oxygen species. In order to reduce the dose of PS administered to patients and hence minimize the harmful side-effects of PDT, new approaches have been devised to increase the effectiveness of tumour-cell killing through targeted delivery of PS to hypersensitive subcellular sites. These approaches are the focus of the present review. Subcellular distribution of photosensitizersInsomuch as most mammalian cells span tens of micrometres, it is clear that PS efficiency will depend not only on the relative distribution of PS between the tumour and surrounding tissues and between malignant and normal cells, but also on the intracellular distribution of the PS. Furthermore, membranes divide the interior of the eucaryotic cell into compartments that differ markedly in their sensitivity to reactions induced by PS-generated reactive oxygen species, in the ability of damaged molecules to be replaced/recycled and in the extent to which such damage affects cell viability and/or the capability of the cell to divide. It is noteworthy that preferential PS accumulation in tumours is itself not a guarantee of selective photoinduced tumour damage and successful PDT. In experiments on rats with gliosarcoma 9L, 10 for example, it has been found that despite a 13-fold higher accumulation of the PS Photofrin in the tumour compared with Summary Photodynamic therapy (PDT) is a novel treatment, used mainly for anticancer therapy, that depends on the retention of photosensitizer...

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Section: Subcellular Redistribution Of Photosensitizers After Photoirmentioning

confidence: 99%

Section: Subcellular Distribution Of Photosensitizers In Vitromentioning

confidence: 99%

Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency

Jans²,

2000

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“…This corresponds to a previous study reporting that the effects of photosensitizers depend on tissue distribution, affinity for certain cell types, penetration into various subcellular compartments, and accumulation [16]. Further, there was the difference between cells due to the various mechanisms involved in cell death [3,17,18]. The phototoxicity at 100 lg/ml of BNCE was higher than ADCL.…”

Section: Bnce Has Toxicity Effects In Dose-dependent Mannermentioning

confidence: 83%

Photodynamic apoptosis and antioxidant activities of Brassica napus extracts in U937 and SK-HEP-1 cells

et al. 2017

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Brassica napus is the most common feedstock for biodiesel production, and its cultivation area has been rapidly increased. Thus, B. napus residues left in the field after harvest are valuable resources. However, there have been few studies on biologically active substances from B. napus plant. The objective of this study is to evaluate cytotoxicity/photodynamic activity and antioxidant activity of B. napus plant extracts. B. napus plants were sequentially extracted with organic solvents (hexane, chloroform, ethanol, and water) and then screened for antioxidant activity and cytotoxicity against leukemia U937 and human liver cancer SK-HEP-1 cells. Among the solvent extracts, the cytotoxicity was the highest when cells treated with chloroform extract and irradiated. Degree of apoptosis substantially increased in both cell types in concentrationdependent manner, and non-irradiated cells showed similar results as the control cells. For the highest concentrations (100 lg/ml), toxicity effect in U937 and SK-HEP-1 cells was 94.62 ± 0.15% and 74.16 ± 1.54%, respectively. We observed the number of cells significantly decreased, and vesicles were floating in B. napus chloroform extract (BNCE) and light condition. BNCE induced DNA laddering pattern (between 300 and 1000 bp) and caspase-3/7 activation in both U937 and SK-HEP-1 cells. Total apoptotic U937 and SK-HEP-1 cells following BNCE 100 lg/ ml and light treatment were significantly increased (92.62 ± 2.07% and 59.71 ± 4.38%, respectively) compared with control. Our results showed that U937 cells were more sensitive than SK-HEP-1 cells. For the antioxidant activity, B. napus ethanol extract was the highest (IC 50 = 0.52 mg/ml).

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“…However, the loss of integrity of intracelullar organelles might result in a redistribution of PS during or after irradiation. PS which are initially localized in lysosomes may be released upon the damage of these and can cause a photodamage to more sensitive organelles such as mitochondria, plasma membrane, nucleus or nucleoli (Ruck et al 1992;Wood et al 1997). Photodamage-induced redistribution of PS from mitochondria to cytoplasm has also been observed (Morgan et al 2000).…”

Section: Mechanisms Of Cell Death As a Function Of Subcellular Localimentioning

confidence: 98%

ROS: Reactive Oxygen Species

김윤미¹,

김영찬²,

정신교³

2013

Encyclopedia of Metalloproteins

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New therapies have been developed using reactive oxygen species produced by light-activation of photosensitizers (PS). Since the lifetime of these species is extremely short and their diVusion in space is limited, the photo-induced reactions primarily aVect the cell organelles labeled by the PS. In addition to the development of molecules with the best optical and photosensitizing properties, considerable research has been done to understand the physico-chemical parameters governing their subcellular localization. In this review, we examine these parameters to establish the structure/eYcacy relationships, which allow speciWc targeting of PS. We examine the eVect of subcellular localization on the cellular response to photosensitization processes. We discuss the determinants of subcellular localization, including the hydrophobic/hydrophilic balance, the speciWc charge eVects and the dynamics of PS' transfer through membranes. SpeciWc targeting can also be achieved with molecular structures able to recognize cellular or intracellular receptors, and this is also dealt with in this paper.

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The Subcellular Localization of Zn(ll) Phthalocyanines and Their Redistribution on Exposure to Light

Cited by 119 publications

References 9 publications

Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency

Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency

Photodynamic apoptosis and antioxidant activities of Brassica napus extracts in U937 and SK-HEP-1 cells

ROS: Reactive Oxygen Species

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