X-ray-induced PDT penetrates to any depth
Multilayer nanoparticles, developed by researchers from the University of Georgia under the leadership of Dr. Jin Xie, allow photodynamic therapy to be used to destroy tumors localized in deep tissues of the body.
Traditional approaches to the treatment of malignant tumors, such as chemo and radiotherapy, damage healthy tissues, causing severe side effects in patients. This problem can be avoided by photodynamic therapy, which has a targeted effect on malignant cells. This approach consists in introducing photosensitizing molecules into the bloodstream or applying them to the patient's skin, which are activated by light of a certain wavelength. As a result of activation, therapeutic molecules transfer part of their energy to oxygen molecules in their immediate vicinity, which leads to the formation of reactive oxygen species that destroy surrounding cells.
However, existing photosensitizers work only under the influence of visible light or near-infrared light, which can penetrate only a few millimeters into the thickness of the tissue. After that, it is absorbed or dispersed. Therefore, traditional photodynamic therapy is applicable only to skin tumors or those located close to the surface of the body.
In order to be able to penetrate into the deep tissues of the body, the researchers set out to create photodynamic agents that are activated by X-rays. Last year, they developed such nanoparticles, but for their activation, an irradiation dose of 5 gray was needed, which corresponds to or even exceeds the usual fractional dose used in traditional radiotherapy.
Not satisfied with the result, the authors decided to develop a more sensitive and clinically suitable photodynamic agent activated by lower doses of X-ray radiation.
They started with a core of europium-activated strontium aluminate (SAO), absorbing X-rays and re-emitting them at longer visible wavelengths. In an aqueous medium, this compound is rapidly hydrolyzed, so it was decided to cover the core consisting of it with a thin layer of solid silicon dioxide (blue), on top of which a layer of mesoporous silicon dioxide (dark gray) was applied. The pores of the outer layer of nanoparticles were filled with the dye mesocyanin (brown spheres), absorbing the light emitted by the nucleus with a wavelength of 540 nanometers and triggering the production of reactive oxygen species (figure from the article in Nano Letters).
The resulting antitumor agent was tested on mice with implanted glioblastomas. The nanoparticle preparation was injected directly into the tumor, after which the injection zone was once exposed to X-ray radiation at a dose of 0.5 gray. 12 days after the procedure, the size of the tumors decreased to 60% of the original size, and after 16 days, some of them were no longer detected. The untreated animals of the control group showed rapid tumor growth. The size of tumors also increased in animals that were exposed to a low dose of X-ray radiation without the introduction of nanoparticles, which indicated that there was no therapeutic effect of irradiation. At the same time, the introduction of nanoparticles did not cause the development of side effects.
Currently, the authors are developing modifications of nanoparticles suitable for injection into the patient's bloodstream and capable of finding a tumor due to antibodies attached to them.
Article by Hongmin Chen et al. Nanoscintillator-Mediated X-ray Inducible Photodynamic Therapy for In Vivo Cancer Treatment is published in the journal Nano Letters.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Chemical & Engineering News:
Nanoparticle Takes Photodynamic Therapy To Deep Tumors.
26.03.2015