Efficacy of photodynamic therapy against doxorubicin-resistant murine tumors

Canti, Gianfranco; Lattuada, D.; Morelli, Susanna; Nicolin, A; Cubeddu, Rinaldo; Taroni, Paola; Valentini, Gianluca

doi:10.1016/0304-3835(95)03818-h

Cited by 34 publications

(24 citation statements)

References 10 publications

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“…[15][16][17][18][19] Milla et al showed that PDT-resistant squamous carcinoma cells had a more¯broblastic morphology, higher number of stress¯bers, more expression of cell-substrate adhesion proteins and higher expression of phospho-survivin but few di®erences in intracellular PpIX content after incubation with ALA methyl derivative. 20 Topical ALA PDT has been successfully used for some resistant cases of cutaneous T-cell lymphoma.…”

Section: Interaction Of Mdr and Psmentioning

confidence: 99%

Photodynamic therapy of cancer — Challenges of multidrug resistance

Huang

Hsu

et al. 2015

J. Innov. Opt. Health Sci.

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can lead to the generation of cytotoxic reactive oxygen species (ROS) and consequently destroy cancer. Similar to many other anticancer therapies, PDT is also subject to intrinsic cancer resistance mediated by multidrug resistance (MDR) mechanisms. This paper will review the recent progress in understanding the interaction between MDR transporters and PS uptake. The strategies that can be used in a clinical setting to overcome or bypass MDR will also be discussed.

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Section: Interaction Of Mdr and Psmentioning

confidence: 99%

Photodynamic therapy of cancer — Challenges of multidrug resistance

Huang

Hsu

et al. 2015

J. Innov. Opt. Health Sci.

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“…Sensitizers may be exogenous (usually porphyrin, phthalocyanine, or chlorophyll derivatives) or endogenous following an injection of 5-amino-levulinic acid to drive a buildup of the active metabolite, protoporphyrin IX. PDT can be used in patients whose condition will not allow for surgery (17,18) and in patients whose cancer has become drug resistant (19,20). Healing is excellent with minimal scaring (1), and repeat treatments do not present problems (1).…”

Section: Photodynamic Therapy (Pdt; Ref 1) Is a Protocol That Usesmentioning

confidence: 99%

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Starkey¹,

Rebane

Drobizhev³

et al. 2008

Clinical Cancer Research

228

189

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Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols. Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT. Results:Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation. Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to singlephoton activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.Photodynamic therapy (PDT; ref. 1) is a protocol that uses light of the appropriate wavelength to activate photosensitizer accumulated in tumor tissue to its triplet state (2). The triplet excitation energy can be effectively transferred to molecular oxygen, resulting in the generation of singlet oxygen, superoxide radical, and other active oxygen species (2, 3). The singlet oxygen causes direct chemical damage to tumor and/or tumor endothelial cells (4), initiates a neutrophilic inflammatory response (5), and can stimulate both innate and specific antitumor immune responses (6 -8). Singlet-oxygen production, however, requires a sufficiently high energy of the triplet state of the sensitizer. Long-wavelength near-IR (NIR) light k ex > 750 nm has relatively low-photon energy, which restricts the range of processes that can be activated by one-photon excitation. The relation between the wavelength and the minimum excitation energy of singlet oxygen is shown in Fig. 1A. The dark gray shaded area corresponds to the excitation energy below the required minimum value, E so < 1.5 -1.6 eV (9, 10), which shows that sensitization by one-photon absorption (1PA) fails in the phototherapeutic window 780 to 950 nm, where tissues have maximum transparency to light. Sensitization by simultaneous two-photon absorption (2PA; ref. 11) combines the energy of two photons and can provide suffi...

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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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Efficacy of photodynamic therapy against doxorubicin-resistant murine tumors

Cited by 34 publications

References 10 publications

Photodynamic therapy of cancer — Challenges of multidrug resistance

Photodynamic therapy of cancer — Challenges of multidrug resistance

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency

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