Utilizing photosensitizing and radiosensitizing properties of TiO2-based mitoxantrone imprinted nanopolymer in fibrosarcoma and melanoma cells.

BACKGROUND: Some materials such as TiO2 display a luminescence property when exposed to X-ray radiation. Therefore, a proper photosensitizer can induce photodynamic effects by absorbing the emitted photons from these materials during radiotherapy. In this way, the problem of limited photo- penetration depth in photodynamic therapy is resolved. In this paper, following the production of a nanopolymer containing TiO2 cores and imprinted for mitoxantron (MIP), the possibility of utilizing its optical and radio properties on two lines of cancer cells were studied. METHODS: Mitoxantron (MX) was selected as the photosensitizer. The emission spectrum of the nanopolymers synthesized with/without MX was recorded during excitation by 6 MV X-rays. Also, the fluorescence signal of hydroxyl radicals produced into terephthalic acid medium by the nanopolymers were recorded during X irradiation. The percentage of cell survival following irradiation by X-rays was determined for various concentrations of drug agents by MTT assay. The synergistic index and IC50 were calculated to compare the findings. RESULTS: The emission spectrum of the nanopolymer reloaded with MX during X-ray irradiation indicated a considerable decline in comparison with the nanopolymer without MX. The level of free radicals produced by nanopolymer was significantly increased during irradiation with X-rays. The highest mean of synergistic indexes was observed in MIP. CONCLUSION: The higher level of hydroxyl free radicals in MIP and lower cell viability in the DFW cell line as well as enhanced treatment efficiency confirm the hypothesis regarding the production of photodynamic effects by synthesized nanopolymer during radiotherapy.

Pegylated hollow gold-mitoxantrone nanoparticles combining photodynamic therapy and chemotherapy of cancer cells.

BACKGROUND: In recent years, Mitoxantrone (MTX) has been introduced as a chemotherapy drug which also serves as a photosensitizer and radiosensitizer. Due to its serious side effects, there are limitations to the application of MTX so scientists are looking for solutions to overcome this problem. Hollow gold nanoparticles (HAuNP) have attracted growing attention due to their unique physical-chemical properties, such as biocompatibility, tunable plasmonic absorption peak ranging from visible to near infrared, high stability and various medical applications in imaging, drug delivery and combinational cancer treatments. In this paper, the combinational effect of photodynamic therapy (PDT) and chemotherapy of MTX conjugated to HAuNP is studied. METHOD: After optimizing the synthesis of PEGylated HAuNP and preparing nanostructures conjugated with MTX, the characteristics of pharmacological agents including MTX, HAuNP, mPEG-HAuNP,and MTX-mPEG-HAuNP and their toxicity were determined at different concentrations on two cell lines of DFW and MCF7 derived from human melanoma and breast cancer, respectively. To select the optimal concentration for PDT, the cytotoxicity of agents was investigated at concentrations of 3, 6, 9 and 12 µM. Moreover, a LEDs system at 630 nm and power output of 3 W was used to apply PDT process. MTT test was used to determine cell survival 24 h after treatment. Several indexes were utilized for data comparison, such as therapeutic efficacy (TE), necessary concentration to kill 50% of cells (IC50), and necessary light exposure to induce 50% cell death (ED50). RESULTS: LED exposure alone did not cause significant cell death. For MTX-mPEG-HAuNP, at both cell lines, IC50 had the least exposure to dark condition with an exposure time of less than 9 min and this nanostructure had the smallest ED50 in each cell line at all concentrations. TE of MTX-mPEG-HAuNP at different exposures and concentrations was greater than 1 for the DFW cells. It was also true for concentrations greater than 6 µM with irradiation times longer than 3 min for MCF7 cells. CONCLUSION: This is the first paper to use PEGylated hollow gold nanoparticles as the nanocarrier for MTX. The results indicated that MTX-mPEG-HAuNP improved the efficacy of PDT with Light Emission diode.

Sonophotodynamic therapy mediated by liposomal zinc phthalocyanine in a colon carcinoma tumor model: Role of irradiating arrangement.

OBJECTIVES: Low penetration depth of light is the main defect of photodynamic therapy (PDT), which could be improved by sonodynamic therapy (SDT). In this study, a combination of PDT and SDT known as sonophotodynamic therapy (SPDT) was investigated using two reverse arrangements in CT26 tumor model. MATERIALS AND METHODS: The liposomal zinc phthalocyanine was synthesized and characterized. It was then administered to CT26 tumor models as a sensitizer. The animal models were subjected to PDT, SDT, and the combined treatment in different groups. The doubling time for the survival of tumors and animals was considered as a measure to evaluate treatments efficacy. RESULTS: In all treatment groups there was a significant decline in tumor volume 15 days after treatment compared to the main control group, but the optimum response was observed in the group receiving a combined treatment with the priority of PDT. 120 days after treatment, in the groups treated by PDT and SDT, the tumor shrank by 20%, while in the group receiving SPDT with PDT priority, 80% of tumors was recovered. No case of complete tumor progression was observed in SPDT group with SDT priority. This could be due to the pores created in cell membranes during ultrasound irradiation of the tumor, which removed the sensitizer molecules from the cells and reduced PDT efficacy in SPDT group with SDT priority. CONCLUSION: It seems that SPDT with PDT priority offers a more efficient alternative than each of PDT, SDT individually or SPDT with the reverse arrangement.

TiO2-based Mitoxantrone Imprinted Poly (Methacrylic acid-co-polycaprolctone diacrylate) Nanoparticles as a Drug Delivery System.

BACKGROUND: Light delivery in photodynamic therapy is a challenging issue in deep cancer treatment. To solve this problem, photosensitizers are conjugated to X-ray luminescent nanoparticles. When the complexes are stimulated by X-rays during radiotherapy, the nanoparticles generate light and activate the photosensitizers. METHOD: Core-shell molecularly imprinted polymers (MIPs) were prepared against mitoxantrone (MX) in which TiO2 nanoparticles were applied as a core, diacrylated polycaprolctone as a biodegradable cross-linker and methacrylic acid (MAA) or 4-vinylpyridin (4-VP) as the functional monomer. TiO2 was selected as a scintillator, MX as a photosensitizer and MIP as a drug delivery system in order to evaluate the possibility of using photodynamic therapy (PDT) during radiotherapy in the next studies. Binding properties of polymers and drug release profile were studied and the optimized MIP was characterized by SEM, TEM, EDS, FT-IR and XRD. Also, cytotoxicity and free radical production were also studied in vitro. RESULTS: Data indicated that MAA-based MIP had superior binding properties compared to its non-imprinted polymer (NIP) and higher imprinting factor value than MIP-4VP. Drug release experiments indicated higher MX released amount from MAA-based MIP than the other polymers. MAA-based MIP was selected as an optimized carrier for MX delivery system. According to the results, the size of MX-MIP@TiO2 was reported to be less than 75 nm. The free radical production and cytotoxicity of nanoparticles were also evaluated in vitro. CONCLUSION: The results of the present work proposed the possibility of applying MIP layer as a drug delivery system around TiO2 nanoparticles.

A comparison of the doses received by normal cranial tissues during different simple model conventional radiotherapeutic approaches to pituitary tumours.

This aim of this study was to compare the doses received by critical cranial organs when three different radiation techniques were used to treat pituitary tumours. Cranial computed tomography scans of a RANDO phantom and 30 patients were used for pituitary macroadenoma radiotherapy treatment planning. For each slice, target volumes and other critical organs were contoured and three techniques were applied: (A) two parallel-opposed lateral fields, (B) two oblique fields (45°) in coronal plane and (C) two parallel-opposed lateral and anterior fields while the head was tilted 45° in the sagittal plane. The doses received by the target volume and the critical organs for each technique were calculated for all patients. Irradiation was repeated three times for each technique. Finally, the doses that reached the organs of interest resulting from these techniques were compared. The dose delivered to the temporal lobes was 105, 9 and 72 % of the prescribed dose using techniques A, B and C, respectively. The dose received by the cochlea was the lowest in technique C (27 % of prescribed dose) compared with techniques A (79 %) and B (48 %). All techniques delivered 100 % of the prescribed dose to the chiasma. Technique A increased the dose to temporal lobes and the cochlea to such an extent that they exceeded the tolerance dose. Technique B spared the temporal lobes better than technique C; however, technique C was preferred since the dose received by the cochlea in this case was the lowest of all techniques. None of the techniques spared the chiasma.