scholarly journals In vivo wireless photonic photodynamic therapy

2018 ◽  
Vol 115 (7) ◽  
pp. 1469-1474 ◽  
Author(s):  
Akshaya Bansal ◽  
Fengyuan Yang ◽  
Tian Xi ◽  
Yong Zhang ◽  
John S. Ho

An emerging class of targeted therapy relies on light as a spatially and temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates light-sensitive drugs, termed photosensitizers, destroying malignant cells without the side effects associated with systemic treatments such as chemotherapy. Effective clinical application of PDT and other light-based therapies, however, is hindered by challenges in light delivery across biological tissue, which is optically opaque. To target deep regions, current clinical PDT uses optical fibers, but their incompatibility with chronic implantation allows only a single dose of light to be delivered per surgery. Here we report a wireless photonic approach to PDT using a miniaturized (30 mg, 15 mm3) implantable device and wireless powering system for light delivery. We demonstrate the therapeutic efficacy of this approach by activating photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by direct illumination, and by delivering multiple controlled doses of light to suppress tumor growth in vivo in animal cancer models. This versatility in light delivery overcomes key clinical limitations in PDT, and may afford further opportunities for light-based therapies.

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 161
Author(s):  
Karin Ried ◽  
Avni Sali ◽  
Michelle Wang ◽  
Brian Meade ◽  
Donald Murphy

Background: An increasing number of patients seek complementary therapies for cancer treatment, the leading cause of death in the developed world. Photodynamic therapy (PDT), the combination of light and a photosensitiser agent, has provided some promising results in cancer therapy. New photosensitiser agents are continuously being developed to improve tolerability and effectiveness. There is a need to objectively evaluate clinical data from PDT patients.Methods: Here we report a case series using the new sublingually administered, chlorophyll-based photosensitiser Photosoft®E4 and an external laser light in a group of ten adult cancer patients not undergoing other concurrent therapies. PDT was administered for three treatment cycles with an average of 14 light treatments per patient, consisting of agent administration and laser treatment on alternate days over 3 months. Safety, tolerability and effectiveness on tumour palliation were monitored. Results: Patients in this study presented with a variety of cancer types and stages; half of the patients had breast cancer, and 40% had metastases. We found Photosoft®E4 to be safe and highly tolerable. However, overall disease status was not improved in our group of patients. Conclusions: Future research is required to determine the bioavailability of Photosoft®E4 and its uptake in tumour tissue, pharmacokinetics and dosing regimen, as well as the best mode of light delivery for the in vivo sensitiser activation.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1762
Author(s):  
Dirk van den Brand ◽  
Sanne A. M. van Lith ◽  
Jelske M. de Jong ◽  
Mark A. J. Gorris ◽  
Valentina Palacio-Castañeda ◽  
...  

Ovarian cancer is the most lethal gynecological malignancy due to late detection associated with dissemination throughout the abdominal cavity. Targeted photodynamic therapy (tPDT) aimed at epithelial cell adhesion molecule (EpCAM), overexpressed in over 90% of ovarian cancer metastatic lesions, is a promising novel therapeutic modality. Here, we tested the specificity and activity of conjugates of EpCAM-directed designed ankyrin repeat proteins (DARPins) with the photosensitizer IRDye 700DX in in vitro and in vivo ovarian cancer models. EpCAM-binding DARPins (Ec1: Kd = 68 pM; Ac2: Kd = 130 nM) and a control DARPin were site-specifically functionalized with fluorophores or IRDye 700DX. Conjugation of anti-EpCAM DARPins with fluorophores maintained EpCAM-specific binding in cell lines and patient-derived ovarian cancer explants. Penetration of DARPin Ec1 into tumor spheroids was slower than that of Ac2, indicative of a binding site barrier effect for Ec1. DARPin-IRDye 700DX conjugates killed EpCAM-expressing cells in a highly specific and illumination-dependent fashion in 2D and 3D cultures. Furthermore, they effectively homed to EpCAM-expressing subcutaneous OV90 xenografts in mice. In conclusion, the high activity and specificity observed in preclinical ovarian cancer models, combined with a high specificity in patient material, warrant a further investigation of EpCAM-targeted PDT for ovarian cancer.


2017 ◽  
Vol 39 (2) ◽  
pp. 117-120
Author(s):  
D A Tzerkovsky

The aim of present study was to investigate an antitumor efficacy of multiple-field interstitial photodynamic therapy (iPDT) in vivo. Materials and Methods: The study was performed on 15 white random-bred rats with subcutaneously transplanted cholangiocellular carcinoma RS-1. Chlorine-based photosensitizer (PS) Ce6CPPPS was administered via single injection at a dose of 2.5 mg/kg into the animal’s caudal vein. Photoirradiation (PI) of tumors was carried out 3 h after PS administration using 7 optical fibers SMA-905 with diode laser with 660 ± 5 nm wavelength at exposure doses of 150 and 300 J/cm² with 0.21 W/cm² fluency rate. The total power density was 360 mW and treatment time was 12 and 24 min. Antitumor efficacy of iPDT was assessed by evaluation of necrosis areas and depth of necrosis in experimental tumors. Results: The results have shown that interstitial PI with multi-field low power density enhanced the antitumor effect of PDT in the RS-1 model. Necrosis areas in tumor tissues after PI with exposure doses 150 and 300 J/cm2 24 h and 96 h after treatment were 83.78 ± 4.25 and 100% (p = 0.00074); 56.79 ± 3.24 and 95.46 ± 1.64% (p < 0.00001), respectively. Conclusion: An analysis of the literature data and the results obtained in this study evidence on high effectiveness of the method of multiple-field.


2014 ◽  
Author(s):  
Raul M Luque ◽  
Mario Duran-Prado ◽  
David Rincon-Fernandez ◽  
Marta Hergueta-Redondo ◽  
Michael D Culler ◽  
...  

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