For photodynamic therapy (PDT), galactose – Lutetium (Lu)-phthalocyanine, as a novel photosensitizer, was administered by intratumoral injection in 8 outbred albino male mice with inoculated hepatoma in a dose of 2 mg/kg. Then, tumors were irradiated through the skin by 670 nm-diode laser source with irradiation dose 200 J /cm2 applied for 1000 sec. The withdrawal of the animals from the experiment and sampling of tissues for morphological study were performed before (n=4) and 72 hrs after PDT (n=4). Tissue of the tumor was taken for morphological examination and fixed in 10% formalin. Serial paraffin sections were stained with hematoxylin-eosin and with the use of immunohistochemical staining with antibodies to proliferation marker Ki-67 and apoptotic marker BAX (Abcam, UK). 3 days after PDT with galactose- Lu-phthalocyanine, pronounced necrotic changes and inflammation reaction were observed in central tumor area, necrosis fields occupied up to 80% of the area. The dystrophic changes, reduction of proliferation degree and development of apoptosis in tumor cells were observed on tumor periphery. The decreased expression of proliferation marker Ki-67 and the increased expression of apoptotic marker BAX were noted in tumor cells after PDT.
The goal of our research was to assess the vascularization degree of tumor to predict the efficiency of plasmonic photothermal therapy (PPT) and photodynamic therapy (PDT) in tumor-bearing rats. Before any treatment, 3D Doppler ultrasound imaging was used for assessment of the vascularization degree of transplanted rat cholangiocarcinoma. For PPT, the gold nanorods with aspect ratio of 4:1, functionalized with thiolated polyethylene glycol, were used. After multiple fractional intravenous (IV) injections in rats with cholangiocarcinoma, the tumours were irradiated through the skin by an 808-nm NIR diode laser at a power density of 2.3 W/cm2 for 15 min. For PDT, galactose – Luphthalocyanine, as a photosensitizer, was applied by intratumoural injection, in a dose of 2 mg/kg. Then, tumors were irradiated through the skin by 670 nm-diode laser source with power density 200 mW/cm2 applied for 1000 sec in three non-overlapping zones covering whole tumour surface to obtain a total irradiation dose of 200 J/cm2 for each lesion. The withdrawal of the animals from the experiment and sampling of tissues for morphological study were performed before and 72 hrs after PPT and PDT. The vascular microdensity in tumors was assessed on histological sections as vessel counts or vessel area per unit of assessed tumor area. It was shown that efficiency of PPT and PDT therapy was mostly due to the sufficient accumulation of photothermosensitizers in the tumor, therefore preliminary assessment of tumor vascularization degree was necessary before starting a therapy.
The paper presents the investigation of change of optical properties of the rat transplanted cholangiocarcinoma doped with gold nanorods after laser-induced plasmon-resonant photothermal treatment (PPT). 72, 48 and 24 hours before the experiment the animals were injected with the suspension of gold nanorods intravenously. For irradiation a diode laser with wavelength 808 nm was used. After the irradiation the tumors and surrounding tissues were removed and sliced. The samples studied were: skin, subcutaneous connective tissue, tumor capsule, top, center, and bottom part of tumor. Spectra of total transmittance and diffuse reflectance of the samples were measured in the wavelength range 350-2250 nm. Absorption and reduced scattering coefficients of the tumor tissues were calculated with inverse adding-doubling method. The results of the experiment were compared with result of investigation of the control tissues without gold nanorods injection and PPT. A decrease in the absorption coefficient of tumor layers in the water absorption bands was obtained, which indicated tissue dehydration during PPT. A decrease in the reduced scattering coefficient of tumor layers indicated an increase in the size of scatterers and an increase in their ordering. Changes in the optical parameters of the skin and subcutaneous layer were insignificant, which indicated a weak thermal damage.
The new generations of photoactive compounds, which are derivatives of already well-established groups of photosensitizers, together with the modern light sources in the spectral region of their activation and in the PDT window range, are emerging as a reliable phototherapy approach for tumour treatment with higher efficiency. The substitution of a highly hydrophobic phthalocyanine with galactose units could improve the solubility and to decrease significant aggregation in polar solvents.
The control group of rats with transplanted cholangiocarcinoma without any treatment was used for comparison of PDT effectiveness. In the second group the white outbred male rats with cholangiocarcinoma lesions were treated using Zn-phthalocyanine, as a typical representative of phthalocyanine photosensitizers with known photodynamic properties and the third group of animals was treated with galactose – Lu-phthalocyanine, as a novel derivative from the same family with two specific differences – presence of galactose and replacing of Zn(II) with Lu(III) ion. To compare the PDT effectiveness of both compounds the same drug doses were applied - 2 mg/kg, applied by intratumoural injection. Diode laser source at 670 nm, on 50 mW output power with power density applied 200 mW/cm2 was applied for 1000 sec to obtain total irradiation dose of 200 J/cm2 for each lesion.
3 days after treatment, the animals were withdrawn from the experiment. Tissue from the central zone and periphery of the tumor was taken for morphological examination and fixed in 10% formalin. Serial paraffin sections were stained with hematoxilin-eosin and by immunohistochemical staining with antibodies to proliferation marker Ki-67 and apoptosis marker BAX. After photodynamic therapy, pronounced necrobiotic changes in combination with an inflammatory reaction were developed at the central zone of tumors. The dystrophic changes, reduction of proliferation and development of apoptosis in tumor cells were observed on tumor periphery as well.
Optical clearing of the human skin under the action of hyaluronic acid (HA) as an enhancer for optical clearing by polyethylene glycol (PEG-300) was studied in vivo by optical coherent tomography (OCT) method on the wavelength 930±5 nm. The results have showed an increase in the transparency of the epidermis at the optical depth of 50±5 μm by 44±9% within 15 min with the use of a solution of HA in combination with sonophoresis before application of PEG-300 to the skin surface. At the same time, when using PEG-300 without preliminary treatment of the skin with the HA, an increase in the transparency of the epidermis at the same depth was 21±8% within 25 min. In dermis at the depth of 500 μm the OCT signal in the experimental group increased more than 1.6 fold what indicates an increasing of optical probing depth.
Nowadays, dynamically developing optical (photonic) technologies play an ever-increasing role in medicine. Their adequate and effective implementation in diagnostics, surgery, and therapy needs reliable data on optical properties of human tissues, including skin. This paper presents an overview of recent results on the measurements and control of tissue optical properties. The issues reported comprise a brief review of optical properties of biological tissues and efficacy of optical clearing (OC) method in application to monitoring of diabetic complications and visualization of blood vessels and microcirculation using a number of optical imaging technologies, including spectroscopic, optical coherence tomography, and polarization- and speckle-based ones. Molecular modeling of immersion OC of skin and specific technique of OC of adipose tissue by its heating and photodynamic treatment are also discussed.
The paper presents the investigation of change of tumor optical properties of the rat tumor doped by gold nanoparticles after laser-induced plasmon-resonant photothermal treatment. To obtain the model tumors the rats have been implanted by suspension of alveolar kidney cancer cells. An hour before the experiment the animals have been injected by the suspension of gold nanorods intratumorally. For irradiation a diode laser with wavelength 808 nm has been used. After the irradiation the tumor has been removed and sliced. Spectra of total and collimated transmission and diffuse reflectance of the samples of different layers of the tumors have been measured in the wavelength range 350-2500 nm. Absorption, scattering, reduced scattering coefficients and scattering anisotropy factor of tumor tissues have been calculated with inverse adding-doubling method. The results of the experiment have shown that after doping the tumor tissue by the plasmon resonant nanoparticles and NIR laser irradiating, there is the decreases of absorption as well as scattering properties of the tumor and surrounding tissues. However, despite the sufficiently high temperature on the surface (about 80°C), the changes in the center of the tumor are insignificant.
Delivery of upconversion microparticles [Y2O3:Yb, Er] and quantum dots (CuInS2/ZnS coated with PEG-based amphiphilic polymer) into rat skin using the fractional laser microablation has been studied in vivo. Luminescence spectroscopy, optical coherence tomography, confocal microscopy, and histochemical analysis were used for visualization of nanoparticles in microchannels. Results have shown that the upconversion microparticles are detected more efficiently in comparison with the quantum dots. The fluorescence intensity of the inserted upconversion microparticles is higher, when the Omnipaque™ was applied as a skin optical clearing agent. The fluorescent images of upconversion nanoparticle distribution indicate the advantage of particle delivery into skin by ultrasound.
Optical clearing of the rat skin under the action of propylene glycol was studied exvivo. It was found that collimated transmittance of skin samples increased, whereas weight and thickness of the samples decreased during propylene glycol penetration in skin tissue. A mechanism of the optical clearing under the action of propylene glycol is discussed. Diffusion coefficient of propylene glycol in skin tissue exvivo has been estimated as (1.35±0.95)×10-7 cm2/s with the taking into account of kinetics of both weight and thickness of skin samples. The presented results can be useful for enhancement of many methods of laser therapy and optical diagnostics of skin diseases and localization of subcutaneous neoplasms.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.