Thomas J. Dougherty: An Appreciation

Kessel, David

doi:10.1111/php.13144

Cited by 11 publications

(32 citation statements)

References 21 publications

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“…Hematoporphyrin derivative or Photofrin 1 was the first PS to be studied in detail . Its chemical structure showed a significant variation between batches and attempts to fractionate it into its individual component molecules frequently yielded mixtures as complicated as the starting material . Other significant deficiencies include (i) long‐lasting skin photosensitivity for up to 8 weeks after administration, (ii) the lack of a reasonably sized absorption band > 650 nm, and (iii) the fact that its tumor‐localizing properties are not as consistent as it is desired.…”

Section: Tetrapyrrole Macrocycles As Psmentioning

confidence: 99%

Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers

et al. 2017

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Photodynamic therapy (PDT) uses non-toxic dyes called photosensitizers (PS) and harmless visible light that combine to form highly-toxic reactive oxygen species that kill cells. Originally a cancer therapy, PDT now includes applications for infections. The most widely studied PS are tetrapyrrole macrocycles including porphyrins, chlorins, bacteriochlorins and phthalocyanines. The present review covers the design features in PS that can work together to maximize the PDT activity for various disease targets. Photophysical and photochemical properties include the wavelength and size of the long-wavelength absorption peak (for good light penetration into tissue), the triplet quantum yield and lifetime, and the propensity to undergo Type I (electron-transfer) or Type II (energy-transfer) photochemical mechanisms. The central metal in the tetrapyrrole macrocycle has a strong influence on the PDT activity. Hydrophobicity and charge are important factors that govern interactions with various types of cells (cancer and microbial) in vitro, and the pharmacokinetics and biodistribution in vivo. Hydrophobic structures tend to be water-insoluble and require a drug delivery vehicle for maximal activity. Molecular asymmetry and amphiphilicity are also important for high activity. In vivo some structures possess the ability to selectively accumulate in tumors, and to localize in the tumor microvasculature producing vascular shutdown after illumination.

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Section: Tetrapyrrole Macrocycles As Psmentioning

confidence: 99%

Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers

et al. 2017

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“…Therefore the use of photosensitizers for bone-marrow purging in the treatment of leukaemias and lymphomas has been explored (reviewed in [20][21][22][23][24]. As such, tumour-cell-specific accumulation of photosensitizers (reviewed in [8,25]), but nevertheless partial eradication of tumour cells with porphyrin derivatives [26][27][28][29] or non-porphyrin photosensitizers, such as merocyanins [30][31][32][33], temoporfin (mthpc) [33], phthalocyanins [34][35][36][37]) and rhodamine [7,23,[38][39][40][41][42] have been reported. Preferential uptake of photosensitizers, including R123, by chronic-myelogeneous-leukaemia cells (CML), have been previously observed [26,27,43,44].…”

Section: Rhodamine Derivatives As Purging Agentsmentioning

confidence: 99%

“…No short-fragment DNA ladder was detected in the few hours following PDP, and 0 % viability was usually only reached after 72 h, suggestive of high-dose ROS necrosis [103] or ROS inhibition of oxidative phosphorylation alone, where cells are dying of apoptosis within days [104]. Other examples of delayed toxicity following mitochondrial damage have been reported [23]. The model is compatible with G 0growth-phase arrest and consequential damage non-repair and cell death [105].…”

Section: Purging Of CML Progenitors From the Graftmentioning

confidence: 99%

“…The mitochondrion is a major player in cell survival and death, necrotis and apoptotis [114]. Cationic dyes usually preferentially target the mitochondrial structure and function [23], which are important sites of action of PSs [23,46,104,[115][116][117][118][119][120]. For TH9402, over 98 % of intracellular fluorescence could be visualized around the mitochondrial membrane by fluorescence microscopy.…”

Section: Mitochondria-mediated Specific Sensitivitymentioning

confidence: 99%

“…Gradual changes MPT development (reviewed in [133][134][135]) until mitochondria succumb to oxidative stress (reviewed in [122,136]) are observed. PDT induces an acute oxidative injury and various cell responses including cell division, differentiation, necrosis and apoptosis, leading to selective death [8,23,137]. Ceramide accumulation may also be a mediator of PDT [138], and CML cells are particularly sensitive to ceramideinduced apoptosis, more than their normal counterparts [82].…”

Section: Mitochondria-mediated Specific Sensitivitymentioning

confidence: 99%

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Ex vivo photodynamic purging in chronic myelogenous leukaemia and other neoplasias with rhodamine derivatives

Villeneuve

1999

Biotech and App Biochem

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Photodynamic therapy (PDT), a cancer treatment already used early in this century, has distinctive advantages over conventional chemotherapy, namely its often observed preferential accumulation in cancer cells and its low intrinsic toxicity. Aggressive therapeutic modalities using high doses of chemotherapy and/or radiation therapy are now commonplace treatments for leukaemia, lymphoma and various non‐haematologic malignancies. These intensive approaches have often been used in association with haematopoietic‐progenitor‐cell support and have induced major responses and remissions in patients with relapsed and refractory diseases, ultimately contributing to improve the disease‐free survival of patients with high risk. This has encouraged Theratechnologies, a Montreal‐based pharmaceutical company, to develop photodynamic ex vivo purging procedures, including the development of new photosensitizers and irradiation devices for the safe eradication of neoplastic cells from autologous grafts. Our first specific objective, therefore, was to design, synthesize, purify and test photoactive rhodamine derivatives. We have also selected a gas and phosphorus coating characteristic of an efficient scanning fluorescent source for extra‐corporeal PDT using rhodamine derivatives. 4,5‐Dibromorhodamine 123 (TH9402) was selected because of its photophysical properties, low toxicity and stability. TH9402 photodynamic‐cell‐therapy process conditions recognized as safe for normal human haematopoietic stem cells and progenitors demonstrated the efficacy of the purging procedure on various leukaemias (including chronic‐myelogenous‐leukaemia as well as non‐Hodgkin‐leukaemias and metastatic‐breast‐cancer cell lines.

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Esterase‐Activated, pH‐Responsive, and Genetically Targetable Nano‐Prodrug for Cancer Cell Photo‐Ablation

Liang

Zhang

Schmidt

et al. 2023

Small

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Thomas J. Dougherty: An Appreciation

Cited by 11 publications

References 21 publications

Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers

Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers

Ex vivo photodynamic purging in chronic myelogenous leukaemia and other neoplasias with rhodamine derivatives

Esterase‐Activated, pH‐Responsive, and Genetically Targetable Nano‐Prodrug for Cancer Cell Photo‐Ablation

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