Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

Kelleher, Debra K.; Bastian, Johannes Dominik; Thews, Oliver; Vaupel, Peter

doi:10.1038/sj.bjc.6601036

Cited by 30 publications

(30 citation statements)

References 42 publications

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“…PDT has the potential to be a powerful treatment modality for cancer either applied solitary or in combination with chemotherapy (16), surgery (17), radiotherapy (18), or other strategies, such as hyperthermia (19). However, low selectivity, inconveniently long drug-light intervals, and prolonged generalized photosensitivity are problems encountered with this therapy modality.…”

Section: Discussionmentioning

confidence: 99%

Optimizing Photodynamic Therapy:In vivoPharmacokinetics of Liposomalmeta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

Buchholz

Kaser‐Hotz²,

Khan

et al. 2005

Clinical Cancer Research

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Purpose: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer. Experimental Design:To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography. The first reports on photodynamic therapy (PDT) date back to the beginning of the last century, when researchers observed that a combination of light with hematoporphyrin induces cell death (1). In 1995, the U.S. Food and Drug Administration approved PDT as a novel form of therapy against cancer, and since then, PDT has been used more frequently.PDT includes two components combined to induce cellular and tissue effects in an oxygen-dependent manner. The first is a ''light-sensitive'' substance called the photosensitizer. The second is light of a specific wavelength (laser light) to maximally activate the tumor-localized photosensitizer. On activation, a photosensitizer undergoes type I (electron or hydrogen transfer) or type II (local generation of cytotoxic singlet oxygen) photochemical reactions.Tumor destruction associated with PDT involves three principal mechanisms (2): (a) direct tumor cell kill (3), (b) destruction of tumor-associated vasculature (4 -6), and (c) activation of an immune response against tumor cells (7,8). A short drug-light interval allows the photosensitizer to accumulate predominantly in the vascular compartment. PDTmediated vascular effects range from transient vascular spasm, vascular stasis, and thrombus formation to total permanent vessel occlusion and can include enhanced vascular leakiness (5). A longer drug-light interval results in maximal concentration of the photosensitizer in the tumor, causing direct tumor cell destruction. This was shown recently for the secondgeneration photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan)] and indicates that the in vivo effects occur via an indirect vascular effect as well as a more direct effect at different drug-light intervals (9, 10).To optimize PDT, liposomes are presently being tested as carrier and delivery systems with the aim of improving the tumoritropic behavior of photosensitizers.

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Section: Discussionmentioning

confidence: 99%

Optimizing Photodynamic Therapy:In vivoPharmacokinetics of Liposomalmeta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

Buchholz

Kaser‐Hotz²,

Khan

et al. 2005

Clinical Cancer Research

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“…Furthermore, the effectiveness of HT combined with other therapies, especially radiotherapy, has been confirmed. Several studies have been performed with combination therapy of HT and PDT for malignant tumors and non-neoplastic diseases, suggesting the effectiveness of HT in combination therapy (11)(12)(13)(14)17,28,29).…”

Section: -------------------------------------------------Table IV Smentioning

confidence: 99%

Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

Yanase¹,

Nomura²,

Matsumura³

et al. 2006

Int J Oncol

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Abstract. In this study, the effectiveness and mechanism of combination therapy of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) with simultaneous hyperthermia (HT) on human-derived osteosarcoma in vivo were examined. A tumor model was prepared by subcutaneously implanting human osteosarcoma into nude mice and local injection of ALA was selected as the administration route. This study demonstrated that both ALA-PDT and the combination of ALA-PDT with HT exhibited significant inhibitory effects on tumor growth. In the group with high total energy, the growth inhibition rates of tumor were 52.3% in ALA-PDT, and 27.3% in ALA-PDT with simultaneous HT (PDT+HT), and the synergetic index was 1.76, demonstrating that the inhibitory effect on tumor growth in ALA-PDT was significantly increased by simultaneous use of HT. In the histological findings, after ALA-PDT, necrosis was observed in the area from the surface to a depth of 2 mm, and only a slight effect was confirmed in deeper layers. On the other hand, after PDT+HT, necrosis was observed in layers even deeper than 2 mm below the surface. Furthermore, based on the immunohistochemical findings of the expression of carbonic anhydrase IX, while weak expression of CAIX was observed after ALA-PDT in an area relatively close to the surface, a positive area extended to the deeper layers after PDT+HT compared with ALA-PDT. In conclusion, PDT+HT demonstrated a significant inhibitory effect on tumor growth of human-derived osteosarcoma, and a synergistic interaction of simultaneous HT. This suggests the possibility that ALA-PDT is useful, not only for the treatment of superficial tumors but also for deep-seated mesenchymal tumors, such as osteosarcoma. Furthermore, the mechanism of the synergistic interaction suggested that ALA-PDT was effective in the deep area of tumors due to the increase of blood flow by mild hyperthermia.

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“…Furthermore, it has been shown that wIRA reduces pain in chronic wounds, warts, herpes, scleroderma, gonarthrosis and spondylitis (Fuchs et al, 2004; Hartel et al, 2006). Applying wIRA would enhance the effects of PDT since heating has some synergistic effect when applied together with PDT (Waldow et al, 1985;Kelleher et al, 2003;Yanase et al, 2006). The use of antimicrobial PDT (APDT) could therefore potentially improve the tissue healing process in a number of dental procedures.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial photodynamic therapy using visible light plus water-filtered infrared-A (wIRA)

Al‐Ahmad

Tennert

Karygianni

et al. 2013

Journal of Medical Microbiology

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The aim of this study was to investigate the effectiveness of antimicrobial photodynamic therapy (APDT) using visible light together with water-filtered infrared-A (VIS+wIRA) to eradicate single species of planktonic bacteria and micro-organisms during initial oral bacterial colonization in situ. A broadband VIS+wIRA radiator with a water-filtered spectrum in the range 580-1400 nm was used for irradiation. Toluidine blue (TB) was utilized as a photosensitizer at concentrations of 5, 10, 25 and 50 mg ml "1 . The unweighted (absolute) irradiance was 200 mW cm "2 and it was applied for 1 min. Planktonic cultures of Streptococcus mutans and Enterococcus faecalis were treated with APDT. Salivary bacteria harvested by centrifugation of native human saliva were also tested. In addition, initial bacterial colonization of bovine enamel slabs carried in the mouths of six healthy volunteers was treated in the same way. Up to 2 log 10 of S. mutans and E. faecalis were killed by APDT. Salivary bacteria were eliminated to a higher extent of 3.7-5 log 10 . All TB concentrations tested proved to be highly effective. The killing rate of bacteria in the initial oral bacterial colonization was significant (P50.004) at all tested TB concentrations, despite the interindividual variations found among study participants. This study has shown that APDT in combination with TB and VIS+wIRA is a promising method for killing bacteria during initial oral colonization. Taking the healing effects of wIRA on human tissue into consideration, this technique could be helpful in the treatment of peri-implantitis and periodontitis. INTRODUCTIONAlthough photodynamic therapy (PDT) is currently being applied in cancer cell elimination (Allison & Sibata, 2010;Ericson et al., 2008), more attention has been paid to its application in antimicrobial treatment (Wood et al., 2006;Donnelly et al., 2007;Maisch, 2007). Due to the growing number of antibiotic-resistant micro-organisms, research is focusing on PDT as an alternative chemotherapy modality (Garcez et al., 2010;Kharkwal et al., 2011). Since PDT causes damage to different parts of microbial cells and affects different interaction pathways in the micro-organisms, the development of antibiotic resistance against PDT can be excluded (Wainwright et al., 2010).PDT impresses with its excellent target-cell specificity and high efficiency. The photodynamic effect requires a photosensitizer, suitable light and oxygen. The photosensitizer can be transferred to the high-energy triplet state and reacts with oxygen, producing singlet oxygen and other radical species which themselves cause increased target cell damage (Konopka & Goslinski, 2007). The photosensitizer should be non-toxic and show antimicrobial activity only after activation by illumination. In addition it should not be bio-destructible. Light sources used in PDT should produce low-power visible light at a specific wavelength (or range of wavelengths) which itself does not harm human tissues in the absence of the photosensitizer. Additionally, light s...

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Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

Cited by 30 publications

References 42 publications

Optimizing Photodynamic Therapy:In vivoPharmacokinetics of Liposomalmeta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

Optimizing Photodynamic Therapy:In vivoPharmacokinetics of Liposomalmeta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

Antimicrobial photodynamic therapy using visible light plus water-filtered infrared-A (wIRA)

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