rus
Issue #8/2013
V.Bakhmetyev, M.Sychov, A.Orlova, E.Potanina, A.Sovestnov, Yu.Kulvelis
Nanophosphors for Rentgenophotodynamic Therapy of Oncological Diseases
Nanophosphors for Rentgenophotodynamic Therapy of Oncological Diseases
Roentgenophotodynamic therapy with the use of a pharmacological preparation containing a photosensitizer and nanophosphor is a complex method for treatment
of oncological diseases. Phosphors have been synthesized
and transform an X-ray radiation into a light with
the necessary lengths of waves. It was demonstrated that
the use of a preparation containing 12 - 16 times
increases the efficiency of destruction of the tumor cells subjected to an X-ray radiation.
of oncological diseases. Phosphors have been synthesized
and transform an X-ray radiation into a light with
the necessary lengths of waves. It was demonstrated that
the use of a preparation containing 12 - 16 times
increases the efficiency of destruction of the tumor cells subjected to an X-ray radiation.
The traditional ways of treatment of malignant tumors are surgical intervention, radiotheraphy, chemotherapy and their com-
binations. Their drawback is a considerable number of complications and a high death rate. For this reason a search for new methods of treatment of oncological diseases and modernization of the existing ones is very important.
One of the effective methods of treatment of the malignant and pretumoral diseases is photodynamic therapy – PDT (fig.1). A photosensitizer is introduced into a patient’s organism, which accumulates selectively in the tumor cells and generates under the influence of light active forms of oxygen (singlet oxygen, peroxides and other similar compounds). After it’s accumulation in a tumor its irradiation by means of a light source is done. Then a photosensitizer begins to generate active oxygen, which destroys the tumor cells.
PDT allows us to cure those patients, for whom the standard methods are inefficient. Application of the method ensures maximal preservation of the healthy tissues, which makes possible to achieve satisfactory therapeutic, functional and cosmetic results. The method allows us to reduce considerably the treatment periods and the number of complications, to restore the patients’ ability to work or shorten their disability periods.
The range of PDT applications is growing. There is a positive domestic experience of treatment of cancer of the cancer of the lung, stomach, esophagus, larynx, breast, bladder, cervix, colon, brain tumors and orbit, basal cell and squamous cell skin cancer. The light sources, as a rule, are lasers or powerful light-emitting diodes, and for delivery of light the quartz fiber-optical light conductors are applied. (fig.1) [1 – 3].
However, notwithstanding all the advantages of PDT, its application for treatment of the cavitary neoplasms is not very affective. The main problem is how to bring the light radiation inside, since the visible light is actively absorbed in the organism’s tissues. Obviously, the PDT method has to be modernized in order to ensure an effective treatment of the oncological neoplasms with a cavitary localization.
The solution of this problem proposed in 2012 by employee of Petersburg Institute of Nuclear Physics Professor DC V.Trunov is create the product which, along with photosensitizer includes a colloidal solution of nanophosphor emitting visible light with the necessary wavelength under the influence of x-ray or gamma radiation, easily penetrating through the tissues of the body.
When such a preparation is introduced into an organism, a local irradiation of a malignant tumor is done, while a the nanophosphor converts all the used kinds of radiation into a visible light, necessary for actionn of the photosensitizer (fig.2).
This phosphor is a low-power light source, which does not cause heating and evaporation of tissues, and, since it is a part of the preparation and has a direct contact with
• The sizes of its particles should not exceed 100 nm (preferably 60–70 nm). It is explained by the fact that before introduction into an organism the preparation containing the photosensitizer and phosphor should be cleaned of microbes. Usually for this purpose a filter with the sizes of cells not more than 100 nm is used. Disinfection of the preparation by boiling is not possible, because it means a thermal destruction of the photosensitizers.
• The luminescence of phosphor should be caused by an x-ray or gamma radiation, easily penetrating through the tissues of an organism.
• The wavelength of the phosphor’s radiation should correspond to one of the strips within the absorption spectrum of the photosensitizer or be close to it as much as possible in order to ensure an effective action of the preparation.
When PDT is applied, usually, for activation of Photoditasine a laser with the wavelength of 661 nm is used as a light source, because of the red light’s higher ability to penetrate into an organism’s tissues. However, the strip with a maximum of 402 nm is more intensive, therefore activation of Photoditasine by a blue light should ensure a more effective generation of the active oxygen, and only poor ability of such a light to penetrate through an organism’s tissues does not allow us to use sources with the given wavelength.
But when the source of light is nanophosphor, the particles of which have a direct contact with the molecules of photosensitizer, the problem of a high absorption of the blue light in an organism does not exist.
The developed technology allows us to obtain nanophosphors based on orthophosphates by their sedimentation from water solutions by the sol gel method. A number of compounds with various cations were synthesized [6–8]. Figure 4 presents spectra of roentgenoluminescence of the synthesized samples of Zn3(PO4)2:Mn2+ and Ba3(PO4)2:Eu2+ compounds, which have the highest luminescence intensity when excited by a hard X-ray radiation with the wavelengths of
0.12–0.31 Å, which corresponds to the radiation of medical therapeutic installations.
It is visible, that the radiation strip of phosphor Zn3(PO4)2:Mn2+ is well collided with a long-wave strip of absorption of Photoditasine, while the radiation strip of phosphor Ba3(PO4)2:Eu2+ – with a short-wave strip of absorption. The synthesized nanophosphors are nontoxic and harmless to organisms.
Figure 5 presents an example of examination of the sizes of Zn3(PO4)2:Mn2+ particles with the help of an atomic-force microscope (АFМ). It was demonstrated that an average size of the particles is equal to 67 nm and meets RPDT requirements to a nanophosphor.
The synthesized phosphor was tested together with a photosensitizer [7] on the cell cultures of fibroblasts of Chinese hamster V-79. A colloidal solution containing these compounds was added to the tumor cells, which were irradiated by a hard X-ray radiation during 1.5 min.
From the table it follows that due to the use of a nanophosphor in combination with a photosensitizer the number of the tumor cells, which survived an irradiation, can be reduced 12–16 times in comparison with the control sample.
In general, use of the synthesized nanophosphors will allow us to develop a unique pharmacological preparation for treatment of oncological diseases by a complex of methods based on the radiation therapy and photodynamic therapy, application of which is expected to raise the efficiency of treatment.
The work was implemented with the support of the Ministry of Education and Science of the RF, Agreement 14.В37.21.1644.
binations. Their drawback is a considerable number of complications and a high death rate. For this reason a search for new methods of treatment of oncological diseases and modernization of the existing ones is very important.
One of the effective methods of treatment of the malignant and pretumoral diseases is photodynamic therapy – PDT (fig.1). A photosensitizer is introduced into a patient’s organism, which accumulates selectively in the tumor cells and generates under the influence of light active forms of oxygen (singlet oxygen, peroxides and other similar compounds). After it’s accumulation in a tumor its irradiation by means of a light source is done. Then a photosensitizer begins to generate active oxygen, which destroys the tumor cells.
PDT allows us to cure those patients, for whom the standard methods are inefficient. Application of the method ensures maximal preservation of the healthy tissues, which makes possible to achieve satisfactory therapeutic, functional and cosmetic results. The method allows us to reduce considerably the treatment periods and the number of complications, to restore the patients’ ability to work or shorten their disability periods.
The range of PDT applications is growing. There is a positive domestic experience of treatment of cancer of the cancer of the lung, stomach, esophagus, larynx, breast, bladder, cervix, colon, brain tumors and orbit, basal cell and squamous cell skin cancer. The light sources, as a rule, are lasers or powerful light-emitting diodes, and for delivery of light the quartz fiber-optical light conductors are applied. (fig.1) [1 – 3].
However, notwithstanding all the advantages of PDT, its application for treatment of the cavitary neoplasms is not very affective. The main problem is how to bring the light radiation inside, since the visible light is actively absorbed in the organism’s tissues. Obviously, the PDT method has to be modernized in order to ensure an effective treatment of the oncological neoplasms with a cavitary localization.
The solution of this problem proposed in 2012 by employee of Petersburg Institute of Nuclear Physics Professor DC V.Trunov is create the product which, along with photosensitizer includes a colloidal solution of nanophosphor emitting visible light with the necessary wavelength under the influence of x-ray or gamma radiation, easily penetrating through the tissues of the body.
When such a preparation is introduced into an organism, a local irradiation of a malignant tumor is done, while a the nanophosphor converts all the used kinds of radiation into a visible light, necessary for actionn of the photosensitizer (fig.2).
This phosphor is a low-power light source, which does not cause heating and evaporation of tissues, and, since it is a part of the preparation and has a direct contact with
• The sizes of its particles should not exceed 100 nm (preferably 60–70 nm). It is explained by the fact that before introduction into an organism the preparation containing the photosensitizer and phosphor should be cleaned of microbes. Usually for this purpose a filter with the sizes of cells not more than 100 nm is used. Disinfection of the preparation by boiling is not possible, because it means a thermal destruction of the photosensitizers.
• The luminescence of phosphor should be caused by an x-ray or gamma radiation, easily penetrating through the tissues of an organism.
• The wavelength of the phosphor’s radiation should correspond to one of the strips within the absorption spectrum of the photosensitizer or be close to it as much as possible in order to ensure an effective action of the preparation.
When PDT is applied, usually, for activation of Photoditasine a laser with the wavelength of 661 nm is used as a light source, because of the red light’s higher ability to penetrate into an organism’s tissues. However, the strip with a maximum of 402 nm is more intensive, therefore activation of Photoditasine by a blue light should ensure a more effective generation of the active oxygen, and only poor ability of such a light to penetrate through an organism’s tissues does not allow us to use sources with the given wavelength.
But when the source of light is nanophosphor, the particles of which have a direct contact with the molecules of photosensitizer, the problem of a high absorption of the blue light in an organism does not exist.
The developed technology allows us to obtain nanophosphors based on orthophosphates by their sedimentation from water solutions by the sol gel method. A number of compounds with various cations were synthesized [6–8]. Figure 4 presents spectra of roentgenoluminescence of the synthesized samples of Zn3(PO4)2:Mn2+ and Ba3(PO4)2:Eu2+ compounds, which have the highest luminescence intensity when excited by a hard X-ray radiation with the wavelengths of
0.12–0.31 Å, which corresponds to the radiation of medical therapeutic installations.
It is visible, that the radiation strip of phosphor Zn3(PO4)2:Mn2+ is well collided with a long-wave strip of absorption of Photoditasine, while the radiation strip of phosphor Ba3(PO4)2:Eu2+ – with a short-wave strip of absorption. The synthesized nanophosphors are nontoxic and harmless to organisms.
Figure 5 presents an example of examination of the sizes of Zn3(PO4)2:Mn2+ particles with the help of an atomic-force microscope (АFМ). It was demonstrated that an average size of the particles is equal to 67 nm and meets RPDT requirements to a nanophosphor.
The synthesized phosphor was tested together with a photosensitizer [7] on the cell cultures of fibroblasts of Chinese hamster V-79. A colloidal solution containing these compounds was added to the tumor cells, which were irradiated by a hard X-ray radiation during 1.5 min.
From the table it follows that due to the use of a nanophosphor in combination with a photosensitizer the number of the tumor cells, which survived an irradiation, can be reduced 12–16 times in comparison with the control sample.
In general, use of the synthesized nanophosphors will allow us to develop a unique pharmacological preparation for treatment of oncological diseases by a complex of methods based on the radiation therapy and photodynamic therapy, application of which is expected to raise the efficiency of treatment.
The work was implemented with the support of the Ministry of Education and Science of the RF, Agreement 14.В37.21.1644.
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