Approaches to targetted photodynamic tumor therapy

Klyashchitsky, B.A.; Nechaeva, I. S.; Ponomaryov, G. V.

doi:10.1016/0168-3659(94)90117-1

Cited by 23 publications

(16 citation statements)

References 31 publications

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“…Binding of synthetic porphyrins to proteins such as human serum albumin, BSA and low‐density lipoproteins has been investigated by several groups [1–3]. Recently porphyrins have been used as photosensitizers in photodynamic therapy (PDT), a new approach developed for the treatment of cancer [4,5]. In PDT, when excited by light of appropriate wavelength, the porphyrin photosensitizers interact with molecular oxygen and convert it to the triplet form, which then reacts with the surrounding tissue and leads to cell death.…”

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confidence: 99%

Thermodynamic and kinetic analysis of porphyrin binding to Trichosanthes cucumerina seed lectin

Kenoth

Reddy

Maiya

et al. 2001

European Journal of Biochemistry

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The interaction of several metallo-porphyrins with the galactose-specific lectin from Trichosanthes cucumeirna (TCSL) has been investigated. Difference absorption spectroscopy revealed that significant changes occur in the Soret band region of the porphyrins upon binding to TCSL and these changes have been monitored to obtain association constants (K a ) and stoichiometry of binding (n ). The dimeric lectin binds two porphyrin molecules and the presence of the specific saccharide lactose did not affect porphyrin binding significantly, indicating that the sugar and the porphyrin bind at different sites. The K a values obtained for the binding of different porphyrins with TCSL at 25 8C were in the range of 2 Â 10 3 25 Â 10 5 M 21 . Association constants for meso-tetra(4-sulphonatophenyl)porphyrinato copper(II) (CuTPPS), a porphyrin bearing four negative charges and meso-tetra(4-methylpyridinium)porphyrinato copper(II) (CuTMPyP), a porphyrin with four positive charges, were determined at several temperatures; from the temperature dependence of the association constants, the thermodynamic parameters change in enthalpy (DH8) and change in entropy (DS8) associated with the binding process were estimated. The thermodynamic data indicate that porphyrin binding to TCSL is driven largely by a favourable entropic contribution; the enthalpic contribution is very small, suggesting that the binding process is governed primarily by hydrophobic forces. Stopped-flow spectroscopic measurements show that binding of CuTMPyP to TCSL takes place by a single-step process and at 20 8C, the association and dissociation rate constants were 1.89 Â 10 4 M 21 : s 21 and 0.29 s 21 , respectively.

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confidence: 99%

Thermodynamic and kinetic analysis of porphyrin binding to Trichosanthes cucumerina seed lectin

Kenoth

Reddy

Maiya

et al. 2001

European Journal of Biochemistry

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“…However, the selectivity of porphyrin compounds towards tumour cells is not always sufficient for PDT to be efficacious. Recently, targeted PDT molecules have been invented by use of special molecules (antibodies or hormones) with photosensitizers aiming to improve their selectivity for tumors (18).…”

Section: Resultsmentioning

confidence: 99%

Interaction of Wheat Germ Agglutinin with Porphyrin Compounds—Potential Anticancer Agents

Bogoeva

Petrova

Ivanov

et al. 2011

Biotechnology & Biotechnological Equipment

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“…The first concerns the development of PDT systems to enhance the efficiency of delivery to target cells. Most (Hamblin and Newman, 1994;Klyashchitsky et al, 1994;Dolmans et al, 2003), but not all (Gijsens et al, 2002;Sharman et al, 2004) targeted PDT studies have used monoclonal antibodies as the address moiety. As the use of antibodies poses several practical limitations (Rihova, 1998), an alternate approach is to target a Tf -Ps conjugate to Tf receptors that are overexpressed on tumour cells (Faulk et al, 1980;Cavanaugh, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…First, whereas Pss tend to accumulate in tumour tissue, their clinical use is often associated with side effects such as cutaneous photosensitivity (Vrouenraets et al, 2003;Sharman et al, 2004). To overcome this problem investigators have covalently linked the Ps to carrier molecules so as to localise the PDT effect (Klyashchitsky et al, 1994;Vrouenraets et al, 2003). One attractive carrier protein -receptor system for this purpose utilises the high-affinity interaction between the iron-transporter transferrin (Tf) and its cell-surface receptor (TfR, CD71).…”

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confidence: 99%

Intracellular chemiluminescence activates targeted photodynamic destruction of leukaemic cells

et al. 2006

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Photodynamic therapy (PDT) involves a two-stage process. A light-absorbing photosensitiser (Ps) is endocytosed and then stimulated by light, inducing transfer of energy to a cytoplasmic acceptor molecule and the generation of reactive oxygen species that initiate damage to cellular membrane components and cytolysis. The expanded use of PDT in the clinic is hindered by the lack of Ps targetcell specificity and the limited tissue penetration by external light radiation. This study demonstrates that bioconjugates composed of transferrin and haematoporphyrin (Tf -Hp), significantly improve the specificity and efficiency of PDT for erythroleukemic cells by a factor of almost seven-fold. Fluorescence microscopy showed that the conjugates accumulate in intracellular vesicles whereas free Hp was mostly membrane bound. Experiments with cells deliberately exposed to Tf -Hp at oLD 100 doses showed that surviving cells did not develop resistance to subsequent treatments with the conjugate. Furthermore, we show that the compound luminol induces intracellular chemiluminescence. This strategy was then used to obviate the use of external radiation for Ps activation by incubating the cells with luminol either before or together with Tf -Hp. This novel chemical means of PDT activation induced cytotoxicity in 95% of cells. These combined approaches provide an opportunity to develop broader and more effective applications of PDT.

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Approaches to targetted photodynamic tumor therapy

Cited by 23 publications

References 31 publications

Thermodynamic and kinetic analysis of porphyrin binding to Trichosanthes cucumerina seed lectin

Thermodynamic and kinetic analysis of porphyrin binding to Trichosanthes cucumerina seed lectin

Interaction of Wheat Germ Agglutinin with Porphyrin Compounds—Potential Anticancer Agents

Intracellular chemiluminescence activates targeted photodynamic destruction of leukaemic cells

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