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Photodynamic therapy applications in gynecologic oncology: new trends?
Abstracts / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375
371
Photodynamic therapy applications in gynecologic oncology: new trends?
The cytotoxic potential of the constructs in target cells was also investigated.
Henri Azaïs 1,2 , Nacim Betrouni 1 , Serge Mordon 1 , Pierre Collinet 1,2
http://dx.doi.org/10.1016/j.pdpdt.2015.07.179
1 INSERM, U1189 - ONCO-THAI, University of Lille, 59000 Lille, France 2 Department of Gynecology, University of Lille, 59000 Lille, France
Ovarian cancer Photodiagnosis has shown a good accuracy to detect peritoneal metastasis of ovarian origin, but therapeutic impact of fluorescence-guided surgery remains uncertain. High peritoneal recurrence rate after optimal treatment raises the issue of peritoneal microscopic disease management and requires the development of additional locoregional treatment strategies. Photodynamic therapy (PDT) ability to treat superficial lesions on large area makes it an excellent candidate to insure destruction of microscopic residual disease in complement of surgery. Molecularly-targeted photosensitizers have a strong clinical potential to improve intraperitoneal PDT therapeutic index. We are currently studying a folate-targeted photosensitizer with promising preclinical results. Endometrial and cervical cancers In early-stage endometrial and cervical cancer (in addition with conisation), PDT could find a place to propose conservative treatment for young women who are eligible for fertility-sparing treatment. Technical aspects Textile light diffusers offer the possibility to apply homogenous light distribution on large surface area (parietal peritoneum). Direct and cylindrical diffusing fibres allow reaching spaces that are difficult to attain. Fluence rates and wavelengths must be adapted to limit light penetration, thus reducing visceral injuries. Light emission monitoring and source tracking are feasible. Combination of spatial tracking and imaging modalities allows a real-time feedback and display of the applied dose. http://dx.doi.org/10.1016/j.pdpdt.2015.07.205 Controlled activation of photosensitizers for site-specific PDT Jordan Atchison 1 , James Davis 2 , John F. Callan 1 1
School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, Northern Ireland 2 School of Engineering, Ulster University, Jordanstown, Northern Ireland One drawback of conventional photodynamic therapy (PDT) is the possible inadvertent activation of the sensitizer in non-target tissue. While careful control of the light source can ameliorate this problem, it can still prove challenging, particularly when considering treatment of internal tumours. Two methods can be exploited to control the production of reactive oxygen species (ROS) reducing the likelihood of ROS production in non-target tissue. These are (i) photoinduced electron transfer (PET) and (ii) Förster resonance energy transfer (FRET). The PET mechanism has previously been shown to control singlet oxygen production, enabling production at acidic pH (typical of cancerous tissue) while minimizing 1 O generation at physiological pH (i.e. normal tissue).[1] Similarly, 2 the FRET mechanism has shown the capability of quenching fluorophore emission at low MMP levels but allowing fluorescence at high MMP levels.[2] This study investigates the ability to control singlet oxygen production from sensitizing drugs through attachment of (a) pH sensitive PET active receptors and (b) a MMP specific peptide armed with quencher dye, to photosensitizer drugs. The ability of the resulting constructs to selectively generate singlet oxygen upon variations in pH or MMP activity was determined.
Antimicrobial Sonodynamic Therapy David Costley, Nigel Ternan, Anthony P McHale, John F Callan School of Pharmacy & Pharmaceutical Science, Ulster University, Coleraine, N. Ireland. The problem of antibiotic resistance has become a worldwide threat to public health. This predicament is exacerbated by the lack of effective novel antibiotic treatments. Antimicrobial Photodynamic Therapy (aPDT) involves light activation of a sensitizer drug to produce cytotoxic radical species and has emerged as a potential alternative to conventional antibiotics, particularly for the treatment of localized infection. However, a major limitation in the effectiveness of treating localized infection using aPDT is the limited penetration of light through human tissue, a feature made even more problematic as many wounds can be highly pigmented due to bruising or scaring. Here, we demonstrate that low intensity ultrasound activation of Rose Bengal and Curcumin generates an antibacterial effect in both Gram-positive and Gram-negative bacteria leading to the complete eradication of bacterial populations. Ultrasound is widely accepted as a cost effective and safe clinical imaging modality and, unlike light, can be tightly focused with penetration in soft tissue up to several tens of centimeters depending on the frequency used. Therefore, our results demonstrate that aSDT has the potential to be used as an antibacterial treatment for use in treating deeply seated infections or in conjunction with aPDT as an adjuvant therapy. http://dx.doi.org/10.1016/j.pdpdt.2015.07.180 The use of surface-modified upconversion nanoparticles for near-infrared-activated photodynamic therapy of oral cancer Patricia SP Thong, Ramaswamy Bhuvaneswari, Pui-Haan Chang, Kar-Perng Low, Niagara M Idris, Ralph M Bunte, Yong Zhang, Khee-Chee Soo Department of Biomedical Engineering, National University of Singapore, Singapore Photodynamic therapy (PDT) is a promising cancer treatment modality. However, it is limited by the penetration depth of the activating light in the visual wavelength range. Up conversion nanoparticles (UCNs) are activated by near-infrared (NIR) light, thereby offering deeper penetration depth for cancer treatment. In this study, we demonstrate the use of surface-modified TiO2coated UCNs for deep penetrating NIR-activated PDT of oral cancer using a mouse model. We studied the uptake and toxicity of the UCNs in the major organs, as well as the efficacy of NIR-PDT against tumors in a xenograft mouse model of oral cancer. The results show that the UCNs were eliminated from the major organs within one week after intravenous administration. Histopathological examination on organ sections did not show any observable abnormalities. In vivo NIR-PDT of oral cancer tumors resulted in elimination or inhibition of tumor growth compared to controls. Surface-modified TiO2-coated UCNs therefore hold promise for therapy of deep-seated or large tumors. http://dx.doi.org/10.1016/j.pdpdt.2015.07.181
371
Photodynamic therapy applications in gynecologic oncology: new trends?
The cytotoxic potential of the constructs in target cells was also investigated.
Henri Azaïs 1,2 , Nacim Betrouni 1 , Serge Mordon 1 , Pierre Collinet 1,2
http://dx.doi.org/10.1016/j.pdpdt.2015.07.179
1 INSERM, U1189 - ONCO-THAI, University of Lille, 59000 Lille, France 2 Department of Gynecology, University of Lille, 59000 Lille, France
Ovarian cancer Photodiagnosis has shown a good accuracy to detect peritoneal metastasis of ovarian origin, but therapeutic impact of fluorescence-guided surgery remains uncertain. High peritoneal recurrence rate after optimal treatment raises the issue of peritoneal microscopic disease management and requires the development of additional locoregional treatment strategies. Photodynamic therapy (PDT) ability to treat superficial lesions on large area makes it an excellent candidate to insure destruction of microscopic residual disease in complement of surgery. Molecularly-targeted photosensitizers have a strong clinical potential to improve intraperitoneal PDT therapeutic index. We are currently studying a folate-targeted photosensitizer with promising preclinical results. Endometrial and cervical cancers In early-stage endometrial and cervical cancer (in addition with conisation), PDT could find a place to propose conservative treatment for young women who are eligible for fertility-sparing treatment. Technical aspects Textile light diffusers offer the possibility to apply homogenous light distribution on large surface area (parietal peritoneum). Direct and cylindrical diffusing fibres allow reaching spaces that are difficult to attain. Fluence rates and wavelengths must be adapted to limit light penetration, thus reducing visceral injuries. Light emission monitoring and source tracking are feasible. Combination of spatial tracking and imaging modalities allows a real-time feedback and display of the applied dose. http://dx.doi.org/10.1016/j.pdpdt.2015.07.205 Controlled activation of photosensitizers for site-specific PDT Jordan Atchison 1 , James Davis 2 , John F. Callan 1 1
School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, Northern Ireland 2 School of Engineering, Ulster University, Jordanstown, Northern Ireland One drawback of conventional photodynamic therapy (PDT) is the possible inadvertent activation of the sensitizer in non-target tissue. While careful control of the light source can ameliorate this problem, it can still prove challenging, particularly when considering treatment of internal tumours. Two methods can be exploited to control the production of reactive oxygen species (ROS) reducing the likelihood of ROS production in non-target tissue. These are (i) photoinduced electron transfer (PET) and (ii) Förster resonance energy transfer (FRET). The PET mechanism has previously been shown to control singlet oxygen production, enabling production at acidic pH (typical of cancerous tissue) while minimizing 1 O generation at physiological pH (i.e. normal tissue).[1] Similarly, 2 the FRET mechanism has shown the capability of quenching fluorophore emission at low MMP levels but allowing fluorescence at high MMP levels.[2] This study investigates the ability to control singlet oxygen production from sensitizing drugs through attachment of (a) pH sensitive PET active receptors and (b) a MMP specific peptide armed with quencher dye, to photosensitizer drugs. The ability of the resulting constructs to selectively generate singlet oxygen upon variations in pH or MMP activity was determined.
Antimicrobial Sonodynamic Therapy David Costley, Nigel Ternan, Anthony P McHale, John F Callan School of Pharmacy & Pharmaceutical Science, Ulster University, Coleraine, N. Ireland. The problem of antibiotic resistance has become a worldwide threat to public health. This predicament is exacerbated by the lack of effective novel antibiotic treatments. Antimicrobial Photodynamic Therapy (aPDT) involves light activation of a sensitizer drug to produce cytotoxic radical species and has emerged as a potential alternative to conventional antibiotics, particularly for the treatment of localized infection. However, a major limitation in the effectiveness of treating localized infection using aPDT is the limited penetration of light through human tissue, a feature made even more problematic as many wounds can be highly pigmented due to bruising or scaring. Here, we demonstrate that low intensity ultrasound activation of Rose Bengal and Curcumin generates an antibacterial effect in both Gram-positive and Gram-negative bacteria leading to the complete eradication of bacterial populations. Ultrasound is widely accepted as a cost effective and safe clinical imaging modality and, unlike light, can be tightly focused with penetration in soft tissue up to several tens of centimeters depending on the frequency used. Therefore, our results demonstrate that aSDT has the potential to be used as an antibacterial treatment for use in treating deeply seated infections or in conjunction with aPDT as an adjuvant therapy. http://dx.doi.org/10.1016/j.pdpdt.2015.07.180 The use of surface-modified upconversion nanoparticles for near-infrared-activated photodynamic therapy of oral cancer Patricia SP Thong, Ramaswamy Bhuvaneswari, Pui-Haan Chang, Kar-Perng Low, Niagara M Idris, Ralph M Bunte, Yong Zhang, Khee-Chee Soo Department of Biomedical Engineering, National University of Singapore, Singapore Photodynamic therapy (PDT) is a promising cancer treatment modality. However, it is limited by the penetration depth of the activating light in the visual wavelength range. Up conversion nanoparticles (UCNs) are activated by near-infrared (NIR) light, thereby offering deeper penetration depth for cancer treatment. In this study, we demonstrate the use of surface-modified TiO2coated UCNs for deep penetrating NIR-activated PDT of oral cancer using a mouse model. We studied the uptake and toxicity of the UCNs in the major organs, as well as the efficacy of NIR-PDT against tumors in a xenograft mouse model of oral cancer. The results show that the UCNs were eliminated from the major organs within one week after intravenous administration. Histopathological examination on organ sections did not show any observable abnormalities. In vivo NIR-PDT of oral cancer tumors resulted in elimination or inhibition of tumor growth compared to controls. Surface-modified TiO2-coated UCNs therefore hold promise for therapy of deep-seated or large tumors. http://dx.doi.org/10.1016/j.pdpdt.2015.07.181