RNA Hydrogel Combined with MnO2 Nanoparticles as a Nano-Vaccine to Treat Triple Negative Breast Cancer

Hypoxia is not only the reason of tumor metastasis but also enhances the spread of cancer cells from the original tumor site, which results in cancer recurrence. Herein, we developed a self-assembled RNA hydrogel that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as MnO2 loaded-photodynamic agent chlorine e6 (MnO2@Ce6), and a chemotherapy drug doxorubicin (DOX) into MDA-MB-231cells. The RNA hydrogel consists of one tumour suppressor miRNA (miRNA-205) and one anti-metastatic miRNA (miRNA-182), both of which showed an outstanding effect in synergistically abrogating tumours. The hydrogel would be dissociated by endogenous Dicer enzyme to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Besides, the hydrogel as the carrier which modified aptamer to targeted MDA-MB-231 has the advantages of good biocompatibility and low cytotoxicity. This strategy could be implemented to design any other microRNA (miRNA) as the carrier, combined with other treatment methods to treat human cancer, thereby overcoming the limitations of current cancer therapies.

Assessment of the photosensitizer efficacy after determination of threshold doses initiating erythrocyte hemolysis

Purpose: To find out a technique for determining the effectiveness of porphyrin-type photosensitizers with concentrations which cause hemolysis in erythrocytes (hemolysis threshold). The hemolysis threshold is found under the following conditions: irradiation in the Soret band with standard parameters – power density, exposure dose, irradiation time.Material and methods. Phototherapeutic device “AST” (LLC “Pankov-medical”) – average power 0.5 W, wavelength ≈ 405 nm. Rat blood erythrocytes. “Multiscan MS” device manufactured by Labsystems, Finland. Preparation “Dimegin”, hematoporphyrin derivative; preparation “Photoditazine” (LLC “VETA-GRAND”), chlorine E6 derivative.Results. On analyzing the results obtained after experimentation with the abovementioned two preparations, it was shown that the developed technique has a high efficacy. It was also shown that the studied photosensitizers are equally effective when irradiated in the Soret band.Conclusion. The developed technique is simple and easy to use. It helps to assess the efficacy of various photosensitizers thus, facilitating the selection of their necessary concentrations for managing different diseases.

EFFECT OF FDT WITH CHLORINE E 6 (X- E 6) ON VIABILITY AND FUNCTIONAL ACTIVITY OF PERIPHERAL BLOOD’S LYMPHOCYTES

We expiremented with mice inoculated with intramuscularly embryocarcinoma and registered functional condition of T-lymphocytic link of cells of bone brain and spleen to the index of spontaneous and stimulated by mitogen (PHA) proliferation. Intact animals and the ones which we introduced with Chlorine e6 and keep in dark conditions have revealed the zero level of the indexes. But the animals being introduced with Chlorine e6 and activated with laser and light-emitting diode radiation have been notable for the index of mitogen (PHA) stimulation. It was established to 25% with the index of spontaneous proliferation remained on zero mark. Animals with embryocarcinoma after FDT with X-e6 with or without glycosamine show immunostimulating effect.

Self-delivery nanomedicine for chemotherapy sensitized photodynamic therapy

A chlorine e6 (Ce6) and curcumain (Cur) based self-delivery nanomedicine (CeCu) is prepared for chemotherapy sensitized photodynamic therapy (PDT). The chemotherapeutic agent of Cur could inhibit the TrxR activity to...

Experimental Approach to the Creation of Efficient Multicomponent Nanocomposites for Antitumor Therapy

Water-soluble polymers with special characteristics can be used as carriers in which the active ingredients are entrapped, encapsulated, adsorbed, or chemically attached. The understanding of the processes occurring during the formation of multicomponent nanosystems is the urgent task for the synthesis of antitumor nanocomposites. Gold nanoparticles (AuNPs), photosensitizer Chlorine e6 (Ce6), and Doxorubicin (Dox) are currently used for the photodynamic therapy and chemotherapy. We have been focused on the study of three-component nanosystems Polymer/AuNPs/Ce6, and four-component nanosystems Polymer/AuNPs/Ce6/Dox at physiological temperatures (37 ∘C). The star-like copolymer with Dextran core and grafted Polyacrylamide chains in nonionic and anionic forms are used as a matrix for the synthesis of nanocomposites. The nanosystems are characterized by the dynamic light scattering and transmission electron microscopy. The increasing of the aggregation processes for the four-component nanosystem Polymer/AuNPs/Ce6/Dox in comparison with the three-component one Polymer/AuNPs/Ce6 is registered. These nanosystems are tested in vitro against the subline of breast carcinoma MCF-7/S – sensitive to cytostatics. It is demonstrated that the increase of the aggregation process occurring in four-component systems leads to the loss of the antitumor activity of multicomponent drugs.

Molecular complexes of chlorin E6 and europium for radiophotodynamic therapy

Фотодинамическая терапия (ФДТ) инновационный метод лечения, применяется, в связи с малой проницаемостью тканей организма для световых квантов лазера, при заболеваниях внешних покровов тела человека (например, меланом и кожных инфекций). Чтобы провести ФДТ опухолей глубинной локализации, нами получены разносоставные многофункциональные комплексы отечественного препарата Фотодитазин (хлорин E6) с европием: бинарный низкоаффинный комплекс хлорина E6 с Eu3 и более стабильный конъюгат, синтезированный на основе полиэтиленимина с ковалентно связанными хлорином E6 (хелатором Eu3) и фолиевой кислотой (для целевой доставки к раковым клеткам с высокой экспрессией рецепторов фолиевой кислоты). Полученные препараты не токсичны в концентрации до 200 мкг/мл. Реактивность хлорина E6 доказана способностью его комплексов к генерации активных форм кислорода (ROS) при УФ-облучении. Передача энергии люминесценции от ионов Eu3 к молекуле хлорина E6 подтверждена при гамма-облучении полученных комплексов. Показано, что доза 2 Гр достаточна для эффективной генерации ROS данными конъюгатами при концентрации 25200 мкг/мл. Это открывает перспективы использования таких препаратов для ФДТ глубинных опухолей при гамма-облучении и, в свою очередь, может повысить результативность стандартной радиотерапии. Photodynamic therapy (PDT) is an innovative method of therapy which is applied due to the low permeability of laser light quanta in the tissues of the body in cases of the outer skin diseases (e.g. melanomas and skin infections). Complexes of the domestic drug Photoditazine (chlorin E6) with europium were produced for PDT of deep-seated tumors. More specifically, a binary low-affinity chlorin E6 complex with Eu3 and a more stable polyethyleneimine-based conjugate with covalently bound E6 chlorin (Eu3 ion chelator) and folic acid as vector for cancer target cells with high expression of folic acid receptors were obtained. The compositions are non-toxic at a concentration up to 200g/ml. The reactivity of chlorine E6 is proved by the ability of its complexes to generate reactive oxygen species (ROS) under UV irradiation. The transfer of luminescence energy from Eu3 ions to the chlorin E6 molecule is confirmed by gamma-irradiation of the obtained complexes. It has been shown that dose 2 Gy is correct for effective generation of ROS by these conjugates at a concentration of 25200 g/ml, which are promising for PDT of deep-seated tumors under gamma irradiation, and, in turn, can increase the effectiveness of standard radiotherapy.