Photodynamic therapy of cancer: Second and third generations of photosensitizers

Wöhrle, Dieter; Hirth, Andreas; Bogdahn-Rai, T.; Schnurpfeil, Günter; Shopova, Maria

doi:10.1007/bf02498146

Cited by 88 publications

(90 citation statements)

References 18 publications

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“…A well-studied porphyrin used in the photosensitized production of singlet oxygen is haematoporphyrin (discussed further in Section 4.2.2). While its triplet quantum yield and singlet oxygen production quantum yields are high (0.83 and 0.65, respectively), its absorption at 630 nm (o 0/3500 M (1 cm (1 ) is weaker than the ideal for a photosensitizer [29].…”

Section: Dyementioning

confidence: 99%

Photosensitized singlet oxygen and its applications

DeRosa

2002

Coordination Chemistry Reviews

2,614

2,134

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Section: Dyementioning

confidence: 99%

Photosensitized singlet oxygen and its applications

DeRosa

2002

Coordination Chemistry Reviews

2,614

2,134

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“…The excited-state dye converts triplet oxygen to the singlet, which is lethal to cells. Light directed into the area of a tumor can lead to the destruction of cancer cells (1,2). One problem in this field is of course the accessibility of tumors to irradiation.…”

mentioning

confidence: 99%

A cyclodextrin dimer with a photocleavable linker as a possible carrier for the photosensitizer in photodynamic tumor therapy

Ruebner

Yang

Leung

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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A cyclodextrin dimer has been synthesized with two ␤-cyclodextrins linked by a flexible chain containing a carbon-carbon double bond. This dimer binds and solubilizes a phthalocyanine-based photosensitizer that generates singlet oxygen on irradiation. When the complex is irradiated, the singlet oxygen cleaves the carbon-carbon link, and the cyclodextrins are released, liberating the photosensitizer into the light path. Ideas about how this phenomenon could be used to make photodynamic tumor therapy into a more selective process are described. In photodynamic therapy, a dye such as a porphyrin or a phthalocyanine is used in conjunction with irradiation, e.g., by visible light. The excited-state dye converts triplet oxygen to the singlet, which is lethal to cells. Light directed into the area of a tumor can lead to the destruction of cancer cells (1, 2). One problem in this field is of course the accessibility of tumors to irradiation. Another problem has to do with the desirability of localizing the photosensitizer at the tumor site to prevent unwanted side reactions elsewhere. An approach to the latter problem has been to target the photosensitizer by using cancerspecific antibodies (3), but this use of a foreign protein may not be ideal.A different approach has been proposed by Moser et al. (4). If a quite hydrophobic photosensitizer is bound to a cyclodextrin (CD) dimer, the complex will become much more hydrophilic, and the strongly bound sensitizer may not be easily taken up by tissues, including those that are not the target tumor cells. However, if the linker in the CD dimer can be cleaved by singlet oxygen, the photosensitizer should be released from the dimer and then enter nearby cells.If this cleavage occurs in the tumor region that is being irradiated, there should be two results. First of all, cleavage of the CD dimer will deliver the photosensitizer to the affected cells, as proposed by Moser et al. (4). Perhaps more interestingly, the destruction of the dimer-sensitizer complex by light will cause more of it to diffuse into the irradiated region, concentrating the sensitizer where it is needed. In other words, the sensitizer will be concentrated into the directed light beam.We have tested this concept by using an electron-rich carboncarbon double bond as the group that is cleavable by singlet oxygen. The oxygen adds to the double bond to form a dioxetane, which fragments to form two carbonyl groups (5). Sulfur substituents at each end of the double bond increase its reactivity. Materials and MethodsCD dimer 1 was synthesized by conversion of cystamine to its N-t-butoxycarbonyl derivative, then reduction of the disulfide link with sodium in ammonia and reaction of the thiolate with cis-1,2-dichloroethylene to form 2 (Scheme 1). All compounds were characterized by NMR and MS, and this olefin 2 had the characteristic infrared signal at 627 cm Ϫ1 for a cis double bond. Acid deprotection of 2 and then acylation with iodoacetic acid anhydride afforded a bis-iodide that was converted to a bisthioacetate. ...

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“…One of the approaches to reach selectivity to malignant cells is based on the synthesis of porphyrins bearing targeting moieties, like carbohydrate moieties (Zheng and Pandey 2008, Aksenova et al 2003, Abrahamse and Hamblin 2016. The preparation of porphyrin-carbohydrate conjugates and the investigation of their ability to target carbohydrate -recognized proteins, which are known for their high expression in certain tumors, might be of great significance (Zhou et al 2016, Hilf 2007, Wöhrle et al 1998, Zheng and Pandey 2008. In fact, the conjugation of carbohydrates to porphyrin derivatives can increase their water solubility and bring better hydrophilic/hydrophobic ratios.…”

Section: Cancer Pdt and Porphyrin-type Derivatives 1003mentioning

confidence: 99%

Cancer, Photodynamic Therapy and Porphyrin-Type Derivatives

Gomes

Cavaleiro

2018

An. Acad. Bras. Ciênc.

113

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This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as photosensitizers in PDT. Intensive studies were performed for almost six decades. The successes really started in 1993 with the first formulation patented under the trade name Photofrin, which was immediately approved in several countries to treat certain types of cancer. Photofrin is still used although certain negative features soon became well known. That has motivated the search for better new photosensitizers. Several ones were developed, evaluated and a few of them had clinical approval. This group includes porphyrin derivatives and pro-drugs (aminolevulinic acid and its alkyl esters). Oncological, dermatological and ophthalmic applications are now taking place for the benefit of mankind. The second part of this review is related with the work carried out in Aveiro at the authors University on the synthesis and biological evaluation of several potential PDT photosensitizers. Not only new synthetic methodologies mainly for porphyrins and chlorins were developed but also other related macrocycles of the phthalocyanine and corrole types have entered in the same "pipeline". In vivo and in vitro biological evaluations also took place under interdisciplinary studies.

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Photodynamic therapy of cancer: Second and third generations of photosensitizers

Cited by 88 publications

References 18 publications

Photosensitized singlet oxygen and its applications

Photosensitized singlet oxygen and its applications

A cyclodextrin dimer with a photocleavable linker as a possible carrier for the photosensitizer in photodynamic tumor therapy

Cancer, Photodynamic Therapy and Porphyrin-Type Derivatives

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