In-vivo optical detection of cancer using chlorin e6 – polyvinylpyrrolidone induced fluorescence imaging and spectroscopy

<p>Abstract</p> <p>Background</p> <p>Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. The purpose of this study was to examine the use of the photosensitizer chlorin e6 (Ce6) formulated in polyvinylpyrrolidone (PVP) as a potential exogenous fluorophore for fluorescence imaging and spectroscopic detection of human cancer tissue xenografted in preclinical models as well as in a patient.</p> <p>Methods</p> <p>Fluorescence imaging was performed on MGH human bladder tumor xenografted on both the chick chorioallantoic membrane (CAM) and the murine model using a fluorescence endoscopy imaging system. In addition, fiber optic based fluorescence spectroscopy was performed on tumors and various normal organs in the same mice to validate the macroscopic images. In one patient, fluorescence imaging was performed on angiosarcoma lesions and normal skin in conjunction with fluorescence spectroscopy to validate Ce6-PVP induced fluorescence visual assessment of the lesions.</p> <p>Results</p> <p>Margins of tumor xenografts in the CAM model were clearly outlined under fluorescence imaging. Ce6-PVP-induced fluorescence imaging yielded a specificity of 83% on the CAM model. In mice, fluorescence intensity of Ce6-PVP was higher in bladder tumor compared to adjacent muscle and normal bladder. Clinical results confirmed that fluorescence imaging clearly captured the fluorescence of Ce6-PVP in angiosarcoma lesions and good correlation was found between fluorescence imaging and spectral measurement in the patient.</p> <p>Conclusion</p> <p>Combination of Ce6-PVP induced fluorescence imaging and spectroscopy could allow for optical detection and discrimination between cancer and the surrounding normal tissues. Ce6-PVP seems to be a promising fluorophore for fluorescence diagnosis of cancer.</p

Photosensitizing effects of chlorin e6 - Polyvinylpyrrolidone for fluorescence guided photodynamic therapy of cancer

Ph.DDOCTOR OF PHILOSOPH

Fiber Optic Spectroscopy for the Optimization of Photodynamic Therapy

__Abstract__ Photodynamic therapy (PDT) is a treatment modality for cancer and premalignant lesions that utilizes a photoactive drug, the photosensitizer, in combination with light. PDT has become the treatment of choice for various malignancies. Furthermore, PDT is under investigation as a potential (palliative) treatment in situations where the possibilities of chemo-­ and radiotherapy are limited or exhausted. Since both photosensitizer and light have to be present to cause tissue damage, selective damage to the lesion can be achieved by controlling the presence of either one of them to the treatment area. Selective damage can be reached by i) choosing a photosensitizer that is mainly present in the lesion, or ii) preventing normal tissue from being illuminated. However, the success of PDT in reducing/removing (pre-­‐)malignant lesions has been variable. Treatment efficacy can range form non-‐observable effects to severe damage to normal tissue. Considering the complexity of both the execution of the treatment and damage pathways involved in PDT, some variability in treatment efficacy is not unexpected. However, given the fact that clinical applications of PDT that have proved successful remain small in number, more work is necessary to optimize therapeutic efficacy

Red haloBODIPYs as theragnostic agents: The role of the substitution at meso position

Three different molecular designs based on BODIPY dye have been proposed as photosensitizers (PSs) for photodynamic therapy (PDT) by the inclusion of halogen atoms (Iodine) at 2,6-positions and with extended conjugation at 3, 5-positions and varying the substitution at meso position. The synthesis is described and their main photophysical features including singlet oxygen production and triplet states were characterized by absorption and fluorescence spectroscopy (steady-state and time-correlated) and nanosecond transient absorption spectroscopy. The results were compared with the commercial Chlorin e6. The three new red-halogen-BODIPYs showed a great balance between singlet oxygen generation (Phi(Delta)>= 0.40) and fluorescence (Phi(fl)>= 0.22) for potential application on PDT, and particularly in theragnosis. In vitro experiments in HeLa cells were done to study their performance and to elucidate the best potential candidate for PDT.This research was funded by the Basque Government, grant numbers IT912-16, IT-1302-19 and IT1639-22. This work is supported by Min-isterio de Ciencia, Innovacion y Universidades-Agencia Estatal de Investigacion (MCI/AEI) , grant numbers MAT2017-83856-C3-2-P and 3-P, PID2020-114347RB-C32, PID2020-114755 GB-C32 and the Uni-versity of the Basque Country (UPV/EHU) , grant number COLAB19/01. R.P.M. thanks UPV/EHU for postdoctoral felowship (DOCREC 20/55) . Open Access funding is provided by University of Basque Country

Photophysical investigation and pharmaceutical applications of chlorin e6 in biodegradable carriers

Ph.DDOCTOR OF PHILOSOPH

New Approaches to Photodynamic Therapy from Type I, II and III to Type IV Using One or More Photons

Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty’s group dating back to the 1970’s. PDT has significant advantages over surgery or radiation therapy for low lying tumours due to better cosmetic outcome and localised treatment for the patients. However, despite these advantages and significant developments in optical technology that has enabled light penetration to deeper lying tumours, in excess of 5 cm, a lack of phase III clinical trials has slowed down the uptake of PDT by the healthcare sector as a frontline treatment in cancer. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold

An effective method to generate controllable levels of ROS for the enhancement of HUVEC proliferation using a chlorin e6-immobilized PET film as a photo-functional biomaterial

Reactive oxygen species (ROS) are byproducts of cellular metabolism; they play a significant role as secondary messengers in cell signaling. In cells, high concentrations of ROS induce apoptosis, senescence, and contact inhibition, while low concentrations of ROS result in angiogenesis, proliferation, and cytoskeleton remodeling. Thus, controlling ROS generation is an important factor in cell biology. We designed a chlorin e6 (Ce6)-immobilized polyethylene terephthalate (PET) film (Ce6-PET) to produce extracellular ROS under red-light irradiation. The application of Ce6-PET films can regulate the generation of ROS by altering the intensity of light-emitting diode sources. We confirmed that the Ce6-PET film could effectively promote cell growth under irradiation at 500 μW/cm2 for 30 min in human umbilical vein endothelial cells. We also found that the Ce6-PET film is more efficient in generating ROS than a Ce6-incorporated polyurethane film under the same conditions. Ce6-PET fabrication shows promise for improving the localized delivery of extracellular ROS and regulating ROS formation through the optimization of irradiation intensity.ope