{"title":"Front Matter: Volume 10860","authors":"","doi":"10.1117/12.2531210","DOIUrl":"https://doi.org/10.1117/12.2531210","url":null,"abstract":"","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"141 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124265835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Lilge, Jenny Wu, A. Manalac, Jeffrey Cassidy, Wayne Embree, Roger White, A. Mandel, Vaughn Betz, M. Jewett, G. Kulkarni
While Photofrin mediated PDT for bladder cancer was the first approved indication for this technique, it failed to attract the confidence of urologists as a treatment option, primarily due to the high incidence of incontinence linked to PDT damage to the bladder muscle. To mitigate this hazard a phase I clinical trial using instillation of the Ru(II) coordination complex TLD1433 and 530 nm activation light was initiated. To achieve the intended drug doses of 0.35 and 0.7 mg/cm2 and a radiant exposure of 90 J/cm2 the concentration of the instillation was adjusted to each patients' bladder volume and the irradiance was measured at up to 12 positions in the bladder. Irradiance monitoring proved helpful in adjusting the irradiation time to the bladder wall albedo and also for increased light scattering and absorption due to turbidity built up in the bladder void. The initial multiplication factors of the bladders (n=6) ranged from 1.1 to 2.8. Monte Carlo simulations based on CT-scans from all 6 participants approximate the range of irradiances observed during these studies. Nevertheless, a fraction of the surface can see a multiple of the average irradiance whereas other regions (typically less than 5% of the surface area) see significantly less than the average irradiance. These variations are due to the actual bladder shape and are somewhat independent of the position of the spherical emitter. Fitting of the measured surface irradiance to the simulated dose surface histograms enables extraction of the bladder wall and bladder void’s optical properties.
{"title":"PDT photo activation irradiance monitoring during a Phase I clinical study of TLD1433 in bladder cancer (Conference Presentation)","authors":"L. Lilge, Jenny Wu, A. Manalac, Jeffrey Cassidy, Wayne Embree, Roger White, A. Mandel, Vaughn Betz, M. Jewett, G. Kulkarni","doi":"10.1117/12.2510888","DOIUrl":"https://doi.org/10.1117/12.2510888","url":null,"abstract":"While Photofrin mediated PDT for bladder cancer was the first approved indication for this technique, it failed to attract the confidence of urologists as a treatment option, primarily due to the high incidence of incontinence linked to PDT damage to the bladder muscle. To mitigate this hazard a phase I clinical trial using instillation of the Ru(II) coordination complex TLD1433 and 530 nm activation light was initiated. To achieve the intended drug doses of 0.35 and 0.7 mg/cm2 and a radiant exposure of 90 J/cm2 the concentration of the instillation was adjusted to each patients' bladder volume and the irradiance was measured at up to 12 positions in the bladder.\u0000Irradiance monitoring proved helpful in adjusting the irradiation time to the bladder wall albedo and also for increased light scattering and absorption due to turbidity built up in the bladder void. The initial multiplication factors of the bladders (n=6) ranged from 1.1 to 2.8. Monte Carlo simulations based on CT-scans from all 6 participants approximate the range of irradiances observed during these studies. Nevertheless, a fraction of the surface can see a multiple of the average irradiance whereas other regions (typically less than 5% of the surface area) see significantly less than the average irradiance. These variations are due to the actual bladder shape and are somewhat independent of the position of the spherical emitter. Fitting of the measured surface irradiance to the simulated dose surface histograms enables extraction of the bladder wall and bladder void’s optical properties.","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126074120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bryan Q. Spring, Kohei Watanabe, Megumi Ichikawa, S. Mallidi, T. Matsudaira, D. Timerman, H. Wakimoto, T. Hasan
{"title":"Targeting drug-resistant glioblastoma stem cells using photodynamic therapy (Conference Presentation)","authors":"Bryan Q. Spring, Kohei Watanabe, Megumi Ichikawa, S. Mallidi, T. Matsudaira, D. Timerman, H. Wakimoto, T. Hasan","doi":"10.1117/12.2510962","DOIUrl":"https://doi.org/10.1117/12.2510962","url":null,"abstract":"","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134063488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. LaRochelle, Kayla Marra, R. E. LeBlanc, M. Chapman, E. Maytin, T. Hasan, B. Pogue
In recent years, numerous publications have documented the growing consensus among dermatologists for daylight-photodynamic therapy (dPDT) treatment of Actinic Kerasotis (AK), with additional evidence supporting treatment of certain non-melanoma skin cancers (NMSC). While these publications aim to address the minimum effective surface-irradiance required for successful clearance, our current work investigates how the tissue optical properties influence the fluence rate within tissue. While it is known red and blue light will have drastically different attenuation profiles in tissue, it is harder to quantify this for broad-spectrum light sources. Our model aims to expand the current PpIX-weighted irradiance metric by incorporating a clinically relevant depth distribution factor. Using a 7-layer skin model, Monte Carlo simulations of optical photons ranging from 350nm – 900nm provide insight into the potential depth of activation of the photosensitizer. Additionally, these models can be applied to known light spectra for both narrow-band conventional treatments (415nm, 633nm), as well as for the Sun and other white light sources (CFL, Halogen). Using this model, we show even when the effective surface-irradiance of the Sun is 4x a halogen light source, the effective fluence within the top 3mm of tissue is generally equivalent, due to the higher proportion of UV-blue light in Sun spectrum which is highly attenuated within the first 50m. We plan to use this model to inform which light source or light combinations would be most appropriate for specific lesion morphologies.
{"title":"Modeling PpIX-effective fluence rate in tissue for multiple light sources used in photodynamic therapy of skin (Conference Presentation)","authors":"E. LaRochelle, Kayla Marra, R. E. LeBlanc, M. Chapman, E. Maytin, T. Hasan, B. Pogue","doi":"10.1117/12.2510162","DOIUrl":"https://doi.org/10.1117/12.2510162","url":null,"abstract":"In recent years, numerous publications have documented the growing consensus among dermatologists for daylight-photodynamic therapy (dPDT) treatment of Actinic Kerasotis (AK), with additional evidence supporting treatment of certain non-melanoma skin cancers (NMSC). While these publications aim to address the minimum effective surface-irradiance required for successful clearance, our current work investigates how the tissue optical properties influence the fluence rate within tissue. While it is known red and blue light will have drastically different attenuation profiles in tissue, it is harder to quantify this for broad-spectrum light sources. Our model aims to expand the current PpIX-weighted irradiance metric by incorporating a clinically relevant depth distribution factor. Using a 7-layer skin model, Monte Carlo simulations of optical photons ranging from 350nm – 900nm provide insight into the potential depth of activation of the photosensitizer. Additionally, these models can be applied to known light spectra for both narrow-band conventional treatments (415nm, 633nm), as well as for the Sun and other white light sources (CFL, Halogen). Using this model, we show even when the effective surface-irradiance of the Sun is 4x a halogen light source, the effective fluence within the top 3mm of tissue is generally equivalent, due to the higher proportion of UV-blue light in Sun spectrum which is highly attenuated within the first 50m. We plan to use this model to inform which light source or light combinations would be most appropriate for specific lesion morphologies.","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"136 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114663613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Personalized strategies for delivering photo therapies to solid tumors with theranostic nanoparticles (Conference Presentation)","authors":"A. Joshi","doi":"10.1117/12.2513587","DOIUrl":"https://doi.org/10.1117/12.2513587","url":null,"abstract":"","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128778864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deep tissue abscesses remain a significant cause of morbidity, mortality, and hospital stay despite improved surgical techniques and use of perioperative antibiotics. Long-term antibiotics increase risk of acquired resistance and polymicrobial infection, limiting future treatment options. We have therefore undertaken a Phase 1 clinical trial to evaluate safety and feasibility of methylene blue mediated photodynamic therapy (MB-PDT) at the time of drainage to treat deep tissue abscesses. This trial uses a fixed photosensitizer dose (1 mg/mL) delivered directly to the abscess cavity, and escalates light dose using a 3+3 design. Three patients were treated at the lowest light dose (20 mW/cm2, 6 J/cm2), with no study-related adverse events. Based on the technical success of this group, recruitment will continue for higher light dose groups with relaxed inclusion criteria. This trial restricts potential subjects to those with single abscesses less than 8 cm in diameter. To investigate MB-PDT feasibility in a wider population, we extracted CT images for patients receiving abscess drainage locally. Images were segmented and imported into a custom Monte Carlo simulation framework. Simulations were performed to determine whether 20 mW/cm2 could be delivered to 95% of the abscess wall, given the available 2 W of optical power at the treatment fiber output. Preliminary results show that this is achievable in 80% of abscesses examined, with volumes ranging from 30-250 mL. Optical power required ranged from 50-950 mW. Based on these initial results, it appears that a large number of abscesses drained may be candidates for MB-PDT.
{"title":"Methylene blue photodynamic therapy for treatment of deep tissue abscess cavities (Conference Presentation)","authors":"T. Baran, M. J. Flakus, H. Choi","doi":"10.1117/12.2506177","DOIUrl":"https://doi.org/10.1117/12.2506177","url":null,"abstract":"Deep tissue abscesses remain a significant cause of morbidity, mortality, and hospital stay despite improved surgical techniques and use of perioperative antibiotics. Long-term antibiotics increase risk of acquired resistance and polymicrobial infection, limiting future treatment options. We have therefore undertaken a Phase 1 clinical trial to evaluate safety and feasibility of methylene blue mediated photodynamic therapy (MB-PDT) at the time of drainage to treat deep tissue abscesses. This trial uses a fixed photosensitizer dose (1 mg/mL) delivered directly to the abscess cavity, and escalates light dose using a 3+3 design. Three patients were treated at the lowest light dose (20 mW/cm2, 6 J/cm2), with no study-related adverse events. Based on the technical success of this group, recruitment will continue for higher light dose groups with relaxed inclusion criteria.\u0000\u0000This trial restricts potential subjects to those with single abscesses less than 8 cm in diameter. To investigate MB-PDT feasibility in a wider population, we extracted CT images for patients receiving abscess drainage locally. Images were segmented and imported into a custom Monte Carlo simulation framework. Simulations were performed to determine whether 20 mW/cm2 could be delivered to 95% of the abscess wall, given the available 2 W of optical power at the treatment fiber output. Preliminary results show that this is achievable in 80% of abscesses examined, with volumes ranging from 30-250 mL. Optical power required ranged from 50-950 mW. Based on these initial results, it appears that a large number of abscesses drained may be candidates for MB-PDT.","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125099413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily Oakley, A. Manalac, Jeffrey Cassidy, L. Lilge, G. Shafirstein
Background and Objectives: Finite Element Methods (FEM) and Monte Carlo (MC, FullMonte) simulations are employed to compute light propagation during interstitial photodynamic therapy. FullMonte models the light source as a fixed number of photons emitted from the center of the catheter. In the FEM, the light source is modeled as a flux of photons emitted from the outside diameter of the catheter. The objective of this study was to compare the FEM and MC computed light fluence rate distributions. Methods: A solid phantom with tissue optical properties was used to compare MC simulations conducted using FullMonte and FEM using COMSOL Multiphysics. A tetrahedral mesh of approximately 400,000 elements was created to mimic experiments in the phantom with one central 2 cm cylindrical diffuser fiber, and five IP85 detector fibers were inserted 5, 10, 15, 20, and 25 mm from the light source. FEM and FullMonte simulations were conducted for 50 and 100 mW/cm source power, and the resulting fluence rates were compared, at the detector locations. Results: Initially, the computed fluence rates differed significantly between the MC and FEM simulations. However, the light gradient was comparable between both methods. Changing the FEM boundary conditions such that the light source was modeled as a flux of photons emitted from inside the catheter approximately 0.6 mm from the outside diameter resulted in a better agreement (16% difference). Conclusions: The light source boundary condition is a major contributor to the difference between FEM and FullMonte computed light distributions. Acknowledgements: This work was supported in part by National Cancer Institute of the National Institutes of Health under Award Number R01CA193610 to G. Shafirstein
{"title":"Comparison of finite element modeling and Monte Carlo simulations for interstitial photodynamic therapy (Conference Presentation)","authors":"Emily Oakley, A. Manalac, Jeffrey Cassidy, L. Lilge, G. Shafirstein","doi":"10.1117/12.2510458","DOIUrl":"https://doi.org/10.1117/12.2510458","url":null,"abstract":"Background and Objectives: Finite Element Methods (FEM) and Monte Carlo (MC, FullMonte) simulations are employed to compute light propagation during interstitial photodynamic therapy. FullMonte models the light source as a fixed number of photons emitted from the center of the catheter. In the FEM, the light source is modeled as a flux of photons emitted from the outside diameter of the catheter. The objective of this study was to compare the FEM and MC computed light fluence rate distributions.\u0000\u0000Methods: A solid phantom with tissue optical properties was used to compare MC simulations conducted using FullMonte and FEM using COMSOL Multiphysics. A tetrahedral mesh of approximately 400,000 elements was created to mimic experiments in the phantom with one central 2 cm cylindrical diffuser fiber, and five IP85 detector fibers were inserted 5, 10, 15, 20, and 25 mm from the light source. FEM and FullMonte simulations were conducted for 50 and 100 mW/cm source power, and the resulting fluence rates were compared, at the detector locations. \u0000\u0000Results: Initially, the computed fluence rates differed significantly between the MC and FEM simulations. However, the light gradient was comparable between both methods. Changing the FEM boundary conditions such that the light source was modeled as a flux of photons emitted from inside the catheter approximately 0.6 mm from the outside diameter resulted in a better agreement (16% difference).\u0000\u0000Conclusions: The light source boundary condition is a major contributor to the difference between FEM and FullMonte computed light distributions. \u0000\u0000Acknowledgements: This work was supported in part by National Cancer Institute of the National Institutes of Health under Award Number R01CA193610 to G. Shafirstein","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128225169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Horgan, Mads S. Bergholt, A. Nagelkerke, I. Pence, U. Kauscher, M. Stevens
{"title":"Combining Raman spectroscopy and photodynamic therapy for optical cancer theranostics (Conference Presentation)","authors":"C. Horgan, Mads S. Bergholt, A. Nagelkerke, I. Pence, U. Kauscher, M. Stevens","doi":"10.1117/12.2507892","DOIUrl":"https://doi.org/10.1117/12.2507892","url":null,"abstract":"","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130220103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Does PDT have a special niche as an affordable technology? (Conference Presentation)","authors":"T. Hasan","doi":"10.1117/12.2515350","DOIUrl":"https://doi.org/10.1117/12.2515350","url":null,"abstract":"","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115261219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandhya Clement, A. Anwer, W. Deng, B. Wilson, C. Allen, E. Goldys
Pancreatic cancer is a highly lethal malignancy and a leading cause of cancer death in the world. Patients are either treated by surgery or by means of radiation therapy or by means of chemotherapy or by combining radiation and chemotherapy together depends upon the status of the pancreatic cancer. All these current treatments have limited efficacy as well as significant toxicity. Photodynamic therapy (PDT) is relatively free from side effects, but it is currently not applicable to pancreatic cancer due to its location in deep tissue. Herein, we developed a PDT system which uses poly (D, L-lactide-co-glycolide) (PLGA) polymeric nanoparticles incorporating a photosensitizer, verteporfin, to generate cytotoxic reactive oxygen species (ROS) by X-ray radiation of 6 MeV. The use of X-ray as the source of energy to trigger verteporfin avoids the limitation of poor penetration depth in conventional PDT. In addition, TAT peptide, a targeting moiety conjugated to the surface of the PLGA nanoconstructs facilitates the targeting of nanoparticles towards the nucleus of the cancer cells. The physiochemical characterisation as well as ROS generation capabilities of the nanoconstructs were studied under 6 MeV X-rays. We believe that the X-ray-induced ROS generation from Verteporfin molecules may be due to Cerenkov radiation (CR) and/or generation of energetic electron by the 6 MeV X-rays which then produce a cascade of ROSs. The cellular experiments carried out in Panc-1 cancer cell line suggest that an improved therapeutic effects can be achieved with the nanoconstructs triggered with X-ray radiation, compared with radiation alone.
胰腺癌是一种高度致命的恶性肿瘤，也是世界上癌症死亡的主要原因。病人要么接受手术治疗，要么接受放射治疗，要么接受化疗，要么接受放疗和化疗相结合，这取决于胰腺癌的状况。目前所有这些治疗方法的疗效有限，而且毒性显著。光动力疗法(PDT)相对来说没有副作用，但由于其位于胰腺深部组织，目前并不适用于胰腺癌。在此，我们开发了一种PDT系统，该系统使用聚(D, l -丙交酯-羟基乙酸酯)(PLGA)聚合物纳米颗粒结合光敏剂，维托泊芬，在6 MeV的x射线辐射下产生细胞毒性活性氧(ROS)。使用x射线作为能量源来触发维替泊芬，避免了传统PDT穿透深度差的限制。此外，结合在PLGA纳米结构表面的靶向片段TAT肽有助于将纳米颗粒靶向癌细胞的细胞核。在6 MeV x射线下研究了纳米结构的理化特性和ROS生成能力。我们认为，x射线诱导的维托波芬分子产生ROS可能是由于切伦科夫辐射(CR)和/或6 MeV x射线产生的高能电子，然后产生级联的ROS。在Panc-1癌细胞系中进行的细胞实验表明，与单独辐射相比，x射线辐射触发的纳米结构可以达到更好的治疗效果。
{"title":"Nuclear targeted x-ray activated photodynamic therapy: a solution to treat pancreatic cancer (Conference Presentation)","authors":"Sandhya Clement, A. Anwer, W. Deng, B. Wilson, C. Allen, E. Goldys","doi":"10.1117/12.2508957","DOIUrl":"https://doi.org/10.1117/12.2508957","url":null,"abstract":"Pancreatic cancer is a highly lethal malignancy and a leading cause of cancer death in the world. Patients are either treated by surgery or by means of radiation therapy or by means of chemotherapy or by combining radiation and chemotherapy together depends upon the status of the pancreatic cancer. All these current treatments have limited efficacy as well as significant toxicity. Photodynamic therapy (PDT) is relatively free from side effects, but it is currently not applicable to pancreatic cancer due to its location in deep tissue. Herein, we developed a PDT system which uses poly (D, L-lactide-co-glycolide) (PLGA) polymeric nanoparticles incorporating a photosensitizer, verteporfin, to generate cytotoxic reactive oxygen species (ROS) by X-ray radiation of 6 MeV. The use of X-ray as the source of energy to trigger verteporfin avoids the limitation of poor penetration depth in conventional PDT. In addition, TAT peptide, a targeting moiety conjugated to the surface of the PLGA nanoconstructs facilitates the targeting of nanoparticles towards the nucleus of the cancer cells. The physiochemical characterisation as well as ROS generation capabilities of the nanoconstructs were studied under 6 MeV X-rays. We believe that the X-ray-induced ROS generation from Verteporfin molecules may be due to Cerenkov radiation (CR) and/or generation of energetic electron by the 6 MeV X-rays which then produce a cascade of ROSs. The cellular experiments carried out in Panc-1 cancer cell line suggest that an improved therapeutic effects can be achieved with the nanoconstructs triggered with X-ray radiation, compared with radiation alone.","PeriodicalId":340377,"journal":{"name":"Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII","volume":"276 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115251773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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