Design of a novel nanoparticle to use X-ray fluorescence of TiO2 to induce photodynamic effects in the presence of PpIX.

BACKGROUND: Radiotherapy and photodynamic therapy are the methods of cancer treatment. Although one limitation of photodynamic therapy (PDT) is the limited penetration depth of light through tissue, using X-rays does not have this restriction. Self-lighting nanoparticles can convert X-rays into UV/visible. This study focuses on a newly designed nanostructure containing mesoporous silica nanoparticles (MSN), titanium dioxide nanoparticles (TiO2, anatase grade), and protoporphyrin IX (PpIX) as a photosensitizer to overcome the limitations of photodynamic therapy. METHODS: After the synthesis and characterization of Ti-MSN/PpIX@PVP nanostructure, two ROSes (OH* and 1O2) were measured when the nanostructures were irradiated with 100 kV and 6 MV photons. The toxicity of Ti-MSN/PpIX@PVP nanostructure in presence and absence of radiation was investigated on DFW and HT-29 cell lines. The in-vitro experiments were analyzed using the MTT assay and colony count assay. Finally, the effect of light exposure in the presence of Ti-MSN/PpIX@PVP nanostructure on the two cell lines was studied. The in-vitro studies were evaluated using the Synergism Index (Syn) and Dose Enhancement Factor (DEF). RESULTS: Based on the FESEM (field emission scanning electron Microscopy) images and DLS (dynamic light scattering) measurements, the size of Ti-MSN/PpIX nanostructure was determined as (35.2 nm) and (168.4 nm), respectively. Based on the spectrofluorimetry results, 100 kV photons produced more ROSes than 6 MV photons. The results of MTT assay and colony formation for X-PDT show Syn >1, except for 100 kV photons for HT-29 cell line. The nanostructure also reduced colony formation induced by X-PDT more effectively when irradiated by 100 kV photons on DFW cells. The results obtained from conventional PDT showed that the ED 50 of the HT-29 cell line was 6 times higher than that of the DFW cell line. CONCLUSION: Designing and synthesizing Ti-MSN/PpIX@PVP nanostructures offer a promising strategy for reducing the current challenges in PDT and for developing and advancing X-PDT as an innovative cancer treatment technique.

A physicochemical model of X-ray induced photodynamic therapy (X-PDT) with an emphasis on tissue oxygen concentration and oxygenation.

X-PDT is one of the novel cancer treatment approaches that uses high penetration X-ray radiation to activate photosensitizers (PSs) placed in deep seated tumors. After PS activation, some reactive oxygen species (ROS) like singlet oxygen (1O2) are produced that are very toxic for adjacent cells. Efficiency of X-PDT depends on 1O2 quantum yield as well as X-ray mortality rate. Despite many studies have been modeled X-PDT, little is known about the investigation of tissue oxygen content in treatment outcome. In the present study, we predicted X-PDT efficiency through a feedback of physiological parameters of tumor microenvironment includes tissue oxygen and oxygenation properties. The introduced physicochemical model of X-PDT estimates 1O2 production in a vascularized and non-vascularized tumor under different tissue oxygen levels to predict cell death probability in tumor and adjacent normal tissue. The results emphasized the importance of molecular oxygen and the presence of a vascular network in predicting X-PDT efficiency.

Cobalt ferrite nanoparticle for the elimination of CD133+CD44+ and CD44+CD24-, in breast and skin cancer stem cells, using non-ionizing treatments.

Background: Cancer stem cells (CSCs) are the most challenging issue in cancer treatment, because of their high resistance mechanisms, that can cause tumor recurrence after common cancer treatments such as drug and radiation based therapies, and the insufficient efficiency of common treatments in CSCs removal and the recurrence of tumors after these treatments, it is essential to consider other methods, including non-ionizing treatments likes light-based treatments and magnetic hyperthermia (MHT). Method and material: After synthesis, characterization and investigation, the toxicity of novel on A375 and MAD-MB-231 cell lines, magnetic hyperthermia and light-based treatments were applied. MTT assay and flow cytometry was employed to determine cell survival. the influence of combination therapy on CD44 + CD24-and CD133 + CD44+ cell population, Comparison and evaluation of combination treatments was done respectively using Combination Indices (CIs). Result: The final nanoparticle has a high efficiency in producing hydroxyl radicals and generating heat in MHT. According to CIs, we can conclude that combined using of light-based treatment and MHT in the presence of final synthesized nanoparticle have synergistic effect and a high ability to reduce the population of stem cells in both cell lines compared to single treatments. Conclusion: In this study a novel multi-functional nanoplatform acted well in dual and triple combined treatments, and showed a good performance in the eradication of CSCs, in A375 and MAD-MB-231 cell lines.

Increased radiosensitivity of melanoma cells through cold plasma pretreatment mediated by ICG.

Radiation therapy (RT) is the primary treatment for many cancers, but its effectiveness is reduced due to radioresistance and side effects. The study aims to investigate an emerging treatment for cancer, cold atmospheric plasma (CAP), as a selectable treatment between cancerous and healthy cells and its role in the occurrence of photodynamic therapy (PDT) utilizing indocyanine green (ICG) as a photosensitizer. We examined whether the efficiency of radiotherapy could be improved by combining CAP with ICG. The PDT effect induced by cold plasma irradiation and the radiosensitivity of ICG were investigated on DFW and HFF cell lines. Then, for combined treatment, ICG was introduced to the cells and treated with radiotherapy, followed by cold plasma treatment simultaneously and 24-h intervals. MTT and colony assays were used to determine the survival of treated cells, and flow cytometry was used to identify apoptotic cells. Despite a decrease in the survival of melanoma cells in CAP, ICG did not affect RT. Comparing the ICG + CAP group with CAP, a significant reduction in cell survival was observed, confirming the photodynamic properties of plasma utilizing ICG. The treatment outcome depends on the duration of CAP. The results for healthy and cancer cells also confirmed the selectivity of plasma function. Moreover, cold plasma sensitized melanoma cells to radiotherapy, increasing treatment efficiency. Treatment of CAP with RT can be effective in treating melanoma. The inclusion of ICG results in plasma treatment enhancement. These findings help to select an optimal strategy for a combination of plasma and radiotherapy.

Effect of photothermal and photodynamic therapy with cobalt ferrite superparamagnetic nanoparticles loaded with ICG and PpIX on cancer stem cells in MDA-MB-231 and A375 cell lines.

BACKGROUND: Cancer cells are resistant to treatments such as chemotherapy and radiotherapy due to their characteristics such as self-renewal, high proliferation and other resistance mechanisms. To overcome this resistance, we combined a light-based treatment with nanoparticles to get advantage of both PDT and PTT in order to increase efficiency and beater outcome. METHODS AND MATERIAL: After synthesis and characterization of CoFe2O4@citric@PEG@ICG@ PpIX NPs, their dark cytotoxicity concentration was determined with MTT assay. Then light-base treatments were performed by two different light source for MDA-MB-231 and A375 cell lines. After treatment, the results were evaluated 48 h and 24 h after treatment by MTT assay and flow cytometry. Among CSCs defined markers, CD44, CD24 and CD133 are the most widely-used markers in CSC research and are also therapeutic targets in cancers. So we used proper antibodies to detect CSCs. Then indexes like ED50, synergism defined to evaluated the treatment. RESULTS: ROS production and temperature increase have a direct relationship with exposure time. In both cell lines, the death rate in combinational treatment (PDT/PTT) is higher than single treatment and the amount of cells with CD44+CD24- and CD133+CD44+ markers has decreased. According to the synergism index, conjugated NPs show a high efficiency in use in light-based treatments. This index was higher in cell line MDA-MB-231 than A375. And the ED50 is proof of the high sensitivity of A375 cell line compared to MDA-MB-231 in PDT and PTT. CONCLUSION: Conjugated NPs along with combined photothermal and photodynamic therapies may play an important role in eradication CSCs.

Opto-microfluidic assisted synthesis of photo-protoporphyrin (pPP) conjugated to hollow gold-albumin hybrid nanoshells to enhance the efficiency of photodynamic therapy of triple negative breast cancer cells.

INTRODUCTION: Protoporphyrin-IX (PpIX), a photosensitizer used in photodynamic therapy, has limitations due to its hydrophobicity, rapid photobleaching, and low absorption peak in the red region. These limitations make the use of PpIX less effective for photodynamic therapy treatments. In this study, we harnessed the power of microfluidic technology to manipulate the properties of PpIX and quickly synthesize albumin-based hybrid nanoshells with high reproducibility. METHODS AND MATERIAL: To begin with, we designed a microfluidic chip with SolidWorksⓇ software; then the chip was fabricated in Poly(methyl methacrylate) (PMMA) material using micromilling and thermal bonding. We synthesized PpIX-loaded CTAB micelles and subsequently transformed the PpIX structure into photo-protoporphyrin (PPP,) by opto-microfluidic chip (Integrating a microfluidic chip with a light source). Simultaneously with CTAB-PPP synthesis complex, we trapped it in binding sites of bovine serum albumin (BSA). Afterward, we used the same method (without irradiating) to generate a hybrid nanostructure consisting of hollow gold nanoshells (HGN) and BSACTAB-PPP. Then, after physical characterization of nanostructures, the photodynamic effects of the agents (HGNs, CTAB-PpIX, BSA-CTABPpIX, HGN-BSA-CTAB-PpIX, CTAB-PPP, BSA-CTAB-PPP, and HGNs-BSA-CTAB-PPP) were evaluated on MDA-MB-231 and 4T1 cells and the cytotoxic properties of the therapeutic agents after treatment for 24, 48, and 72 hours were investigated using MTT assay. Finally, we analyzed the findings using GraphPad Prism 9.0 software. RESULTS: Results revealed that the opto-microfluidic assisted synthesis of HGN-BSA-CTAB-PPP is highly efficient and reproducible, with a size of 120 nm, a zeta potential of -16 mV, and a PDI index of 0.357. Furthermore, the cell survival analysis demonstrated that the HGNBSA-CTAB-PPP hybrid nanostructure can significantly reduce the survival of MDA-MB-231 and 4T1 cancer cells at low radiation doses (< 10 J/cm2) when exposed to an incoherent light source due to its strong absorption peak at a wavelength of 670 nm. CONCLUSION: This research indicates that developing albumin-based multidrug hybrid nanostructures using microfluidic technology could be a promising approach to design more efficient photodynamic therapy studies.

Optimization of cobalt ferrite magnetic nanoparticle as a theranostic agent: MRI and hyperthermia.

OBJECTIVE: Magnetic nanoparticles (MNPs) are considered a theranostic agent in MR imaging, playing an effective role in inducing magnetic hyperthermia. Since, high-performance magnetic theranostic agents are characterized by superparamagnetic behavior and high anisotropy, in this study, cobalt ferrite MNPs were optimized and investigated as a theranostic agent. METHODS: CoFe2O4@Au@dextran particles were synthesized and characterized by DLS, HRTEM, SEM, XRD, FTIR, and VSM methods. After cytotoxicity evaluation, MR imaging parameters (r1, r2 and r2 / r1) were calculated for these nanostructures. Afterward, magnetic hyperthermia at the frequency of 425 kHz was applied to calculate specific loss power (SLP). RESULTS: Formation of CoFe2O4@Au@dextran was confirmed by UV-Visible spectrophotometry. On the basis of the relaxometric and hyperthermia induction findings of nanostructures in all stages of synthesis, the CoFe2O4@Au@dextran could produce the highest parameters of r2 and r2/r1 and SLP with values ​​of 389.7, 51.2 mM-1 s-1, and 2449 W/g, respectively. CONCLUSION: The formation of multi-core MNPs by dextran coating is expected to improve the magnetic properties of the nanostructure, leading to optimization of theranostic parameters, so that CoFe2O4@Au@dextran NPs can create contrast-enhanced images more than three times the clinical use and require less contrast agent, reducing side effects. Accordingly, CoFe2O4@Au@dextran can be introduced as a suitable theranostic nanostructure with optimal efficiency.

In vivo evaluation of Sono-chemo therapy via hollow gold nanoshells conjugated to mitoxantrone on breast cancer.

Objectives: Conventional methods of cancer treatment include surgery, chemotherapy, radiation therapy, and immunotherapy. Chemotherapy, as one of the main methods of cancer treatment, due to the lack of targeted distribution of the drug in tumor tissues, is not able to destroy cancer cells and also affects healthy tissues and causes serious side effects in patients. Sonodynamic therapy (SDT) is a promising strategy for non-invasive treatment of deep solid cancer tumors. In this study, for the first time, the sono-sensitive activity of mitoxantrone was investigated and then mitoxantrone (MTX) was conjugated to hollow gold nanostructure (HGN) to improve the efficiency of in vivo SDT. Materials and Methods: Firstly, after the synthesis of hollow gold nanoshells and the PEGylation process, conjugation of MTX was performed. Then, after evaluating the toxicity of the treatment groups in vitro, in order to perform an in vivo study, 56 male Balb/c mice that had been tumorized by subcutaneous injection of 4T1 cells were divided into eight groups of breast tumor model. Ultrasonic irradiation (US) conditions including intensity of 1.5 W/cm2 (with a frequency of 800 kHz, 5 min), MTX concentration of 2 µM, and HGN dose of 2.5 mg/kg (unit of animal weight) were used. Results: The results show that administration of PEG-HGN-MTX caused a slight reduction in tumor size and growth compared with free MTX. Ultrasound also improved the therapeutic effect of the gold nanoshell in treated groups, and the HGN-PEG-MTX-US treated groups were able to significantly reduce and control tumor size and growth. Conclusion: The findings also show that MTX and HGN can be used as sonosensitizers in SDT. Also, HGN-PEG-MTX can act as a sono-chemotherapy agent for the combination of sonodynamic therapy and chemotherapy for in vivo breast tumors.

The multimodal effect of Photothermal/Photodynamic/Chemo therapies mediated by Au-CoFe2O4 @Spiky nanostructure adjacent to mitoxantrone on breast cancer cells.

BACKGROUND: Conventional cancer treatments are associated with a number of limitations, including non-selectivity, toxicity and multidrug resistance, so new nanotechnologies are being developed forcancer diagnosis and therapy. Phototherapy approach based on nanotechnology is a hopeful strategy to overcome these problems. Photothermal (PTT) and photodynamic therapies (PDT), in addition to having non-invasive properties, are known as promising methods for treatment of tumors. In this study, CoFe2O4 theranostic magnetic nanoparticles coated with spiky gold nanoparticles were designed and synthesized and its photothermal effects were evaluated in combination with the photodynamic and chemotherapeutic effects of mitoxantrone (MTX) under in vitro conditions. METHODS AND MATERIALS: At first, CoFe2O4 @Spiky Au nanostructure was synthesized and after its characterization, cytotoxicity of MTX, CoFe2O4 @ Spiky Au (MGNS) and CoFe2O4 @ Au were determined on MDA-MB-231 cell line. Then, the concentrations required for inducing 50% cell death (IC50) and appropriate concentration for this study was obtained. Cells were irradiated by an 808 nm laser and a non-synchronous light source at 670 nm at the separate groups. The viability of treated cells was determined via MTT test 48 h after treatment. RESULTS: In the groups receiving energy density (5-40) J/cm2, at the lower laser dose an increase in cell survival was observed (P < 0.05) and then cell survival was decreased (P < 0.05). In the groups receiving non-coherent light (2-18 J/cm2) from the beginning, a decreasing trend in cell survival is observed. CONCLUSION: The overlap of the emission spectrum of the light source and the absorption spectrum of the nanostructure amplified the cell death. Similar to the Hormesis model reported for ionizing radiation effects, at low light doses with the bio-phasic response dose model, increased cell survival and proliferation can be expected.

The Synergistic Effect of Cold Atmospheric Plasma Mediated Gold Nanoparticles Conjugated with Indocyanine Green as An Innovative Approach to Cooperation with Radiotherapy.

OBJECTIVE: The multimodality treatment of cancer provides a secure and effective approach to improve the outcome of treatments. Cold atmospheric plasma (CAP) has got attention because of selectively target and kills cancer cells. Likewise, gold nanoparticles (GNP) have been introduced as a radiosensitizer and drug delivery with high efficacy and low toxicity in cancer treatment. Conjugating GNP with indocyanine green (ICG) can develop a multifunctional drug to enhance radio and photosensitivity. The purpose of this study is to evaluate the anticancer effects of GNP@ICG in radiotherapy (RT) and CAP on DFW melanoma cancer and HFF fibroblast normal cell lines. MATERIALS AND METHODS: In this experimental study, the cells were irradiated to RT and CAP, alone and in combination with or without GNP@ICG at various time sequences between RT and CAP. Apoptosis Annexin V/PI, MTT, and colony formation assays evaluated the therapeutic effect. Finally, the index of synergism was calculated to compare the results. RESULTS: Most crucially, the cell viability assay showed that RT was less toxic to tumors and normal cells, but CAP showed a significant anti-tumor effect on melanoma cells with selective toxicity. In addition, cold plasma sensitized melanoma cells to radiotherapy so increasing treatment efficiency. This effect is enhanced with GNP@ICG. In comparison to RT alone, the data showed that combination treatment greatly decreased monolayer cell colonization and boosted apoptotic induction. CONCLUSION: The results provide new insights into the development of better approaches in radiotherapy of melanoma cells assisted plasma and nanomedicine.

Surface modification of gold nanoparticles with 6-mercapto-1-hexanol to facilitate dual conjugation of protoporphyrin IX and folic acid for improving the targeted photochemical internalization.

Objectives: Photochemical internalization (PCI) is an important type of photodynamic therapy for delivering macromolecules into the cytosol by the endocytosis process. In this study, 6-mercapto-1-hexanol (MH) was used to functionalize the gold nanostructure as a primer for surface modification to improve conjugation of multi-agents such as protoporphyrin IX (Pp-IX) and folic acid with gold nanoparticles (PpIX/FA-MH-AuNP) to facilitate the photochemical internalization. Materials and Methods: After surface modification of AuNPs with MH, PpIX and FA are bonded to the surface of the MH-AuNPs through the coupling reaction to produce the desired conjugated AuNPs. In the next step, the synthesized nanostructures were characterized by different methods. Finally, after selecting specific concentrations, light treatments were applied and cell survival was measured based on MTT analysis. Also, in order to better study the morphology of the cells, they were stained by the Giemsa method. The SPSS 16 software was used for data analysis. Results: By surface modification of the nanostructure with MH and then conjugation of FA to it, the incubation time of the drug in PpIX/FA-MH-AuNP was reduced from 3 hr to 30 min. Also, at each light dose, cell death in the presence of PpIX/FA-MH-AuNP was significantly reduced compared with unconjugated conditions (P<0.001). Under these conditions, the ED50 for PpIX and PpIX-MH-AuNP and PpIX/FA-MH-AuNP at a concentration of 2.5 µg/ml is 8.9, 9.1, and 6.17 min, respectively. Conclusion: The results show that the PCI of PpIX/FA-MH-AuNP increases the selective phototoxicity efficiency on cancer cells compared with the conventional process of photodynamic therapy.

In vitro evaluation of the intensifying photodynamic effect due to the presence of plasmonic hollow gold nanoshells loaded with methylene blue on breast and melanoma cancer cells.

BACKGROUND: Hypoxia is one of the most important limiting factors in photodynamic therapy that can reduce the effectiveness of this treatment. By designing a nanocomplex of plasmonic nanoparticles and photosensitizers with similar optical properties, the rate of free oxygen radical production can be increased and the efficiency of photodynamic therapy can be improved. in this study, we tried to use the outstanding capacities of hollow gold nanoshells (HGNSs) as a plasmonic nanocarrier of methylene blue (MB) to improve the performance of photodynamic therapy. METHODS AND MATERIAL: After synthesis and optimization of hollow gold nanoshells loaded with Methylene blue (HGNSs-PEG-MB), the characteristics of MB, HGNSs, HGNSs-PEG, HGNSs-PEG-MB, and their toxicity at different concentrations on the cell lines was determined. After determining of optimum concentration of nano agents, irradiation of cell was performed with non-coherent of light source with 670 nm wavelength and an intensity of 14.9 mW/cm2. Twenty-four hours after irradiation, an MTT assay was used to determine cell survival percentage. To compare the results, we defined different indexes such as treatment efficiency (TE), synergism ratio (SYN), and the amount of exposure required for 50% cell death (ED50). All the tests were repeated at least four times on the DFW and MCF-7 cancer cell lines. RESULTS: For combination therapies with Lumacare irradiated HGNSs-PEG-MB, the UC index was less than one for all concentrations (P < 0.05). Also, the IC50 index for this nanostructure in non-irradiated conditions and less than 9 min irradiation time was lower than other treatment groups (P < 0.05). ED50 amounts for HGNSs-PEG-MB in all concentrations were greater than the other groups. TE Index was also reported to be greater than 1 in all irradiation conditions and concentrations. CONCLUSION: In this study, HGNSs-PEG in the role of nanocarriers for methylene Blue was used. The results showed that irradiated HGNSs-PEG-MB by 670 nm light severely induced cell death and greatly improved the efficiency of photodynamic therapy in melanoma and breast cancer cells.

Evaluating the efficacy of photodynamic therapy with indocyanine green in the treatment of keloid.

BACKGROUND: This study aimed to evaluate the efficacy of photodynamic therapy (PDT) with topical indocyanine green (ICG) in the treatment of keloid lesions. METHODS: In this pilot study, fifteen keloids (6 lesions on the sternal area, 3 on the shoulders, 2 on the abdomen, 2 on the legs, and 2 on the forearms) were selected. To enhance drug penetration, pretreatment with CO2 laser was performed. Then Lesions were covered with 0.2% transfersomal ICG gel with 1 mm thickness and occluded with light-proof plastic nylon for 2 h. Afterward, it was wiped off and underwent photodynamic therapy with source LumaCare with 730 nm probe and fluence of 23 J/cm2 every week for 6 sessions. Patients were also assessed 6 and 12 weeks after the treatment for any recurrences. The Patient and Observer Scar Assessment Scale (POSAS) was used to evaluate the scars. RESULTS: The mean POSAS score significantly reduced by 23.69% from 46.86 at baseline to 35.76 at the 6th treatment session (P< 0.001). The mean scores of patient and observer overall opinion significantly decreased by 16.35% (P< 0.001) and 12.31% (P = 0.001) respectively. No side effects were observed during treatment and after 3 months of follow-ups. After discontinuation of therapy, the mean score of POSAS significantly increased by 13.77% to 40.80. (P = 0.001) CONCLUSION: According to our study, ICG-PDT is an effective and safe treatment for keloid. However, due to the recurrence following discontinuation of treatment, further studies are needed.

Evaluation of photodynamic effect of Indocyanine green (ICG) on the colon and glioblastoma cancer cell lines pretreated by cold atmospheric plasma.

BACKGROUND: Cold Atmospheric Plasma (CAP) has been proposed as a new approach based on its anticancer potential. However, its biological effects in combination with other physical modalities may also enhance efficiency and expand the applicability of the CAP method Photodynamic Therapy (PDT) may be improved by the use of indocyanine green (ICG) photosensitizer with absorption wavelength in the near infrared region to allow for deeper treatment depth.. In this study, the effectiveness of cold atmospheric helium plasma (He-CAP) as a pretreatment on the efficiency of ICG mediated PDT was investigated. METHODS AND MATERIAL: First, toxicity of different concentrations of ICG on HT-29 and U-87MG cell lines was examined for 24 h. IC10 and IC30 of ICG were determined and then cells were treated with this ICG concentrations with different plasma radiation doses and light exposures for 48 h. Finally, MTT assay was performed for all treatment groups. The experiments were repeated at least 4 times at each group for two cell lines, separately. In order to compare the results, several indicators such as treatment efficiency, synergistic ratio, and the amount of optical exposure required for 50% cell death (ED50) were also defined. Finally, SPSS 20 software is used for statistical analysis of data. RESULTS: Pretreatment with CAP could significantly reduce cell survival in both cell lines (P<0.05). Also concentrations, irradiation time with CAP, and appropriate light exposure in both cell lines increased therapeutic efficiency compared to either treatment alone (P<0.05). While increasing the efficiency of photodynamic therapy varied between the two cell lines, the improvement in the PDT process was demonstrated by pretreatment with CAP. CONCLUSION: Synergistic effect in the cell death with PDT were observed following He-CAP treatment and the results indicated that pretreatment with He-CAP improves the efficiency of photodynamic therapy.

Accompanying photocytotoxic activity of gold nanoechinus and zinc phthalocyanine on cancerous cell lines.

BACKGROUND: Near-infrared triggered photodynamic therapy (NIR-PDT) has been introduced as a relatively deep tumor treatment modality. The gold Nanoechinus (Au NE) is a rare type of nanostructures that act as a transducer to change NIR wavelength to ultraviolet (UV) and visible lights. During the photodynamic process, Au nanoechinus (Au NE) converts the irradiation of 980 nm to 674 nm which is absorbed by Zn(II) Phthalocyanine tetrasulfonic acid (ZnPcS). In this study the cooperation effect of Au NE and ZnPcS in PDT on MCF7 and Hela cells was investigated. METHODS: Cytotoxicity and phototoxicity of the composition having different concentrations of Au NE and ZnPcS upon irradiation of 980 nm NIR light were evaluated against MCF7 and Hela cells after two different incubation times and irradiating with two different power densities of laser. RESULTS: Among different experimental groups, in MCF7 cells, which were incubated for 48 h with 50 µg/mL Au NE+2µM ZnPcS and were treated by 980 nm laser with a power density of 200 mW cm-2 for 15 and 30 min, 48 and 38% cell viability were recorded. No appreciable result was observed due to PDT of Hela cells. CONCLUSIONS: Comparing to other PDT modalities against MCF7 cells, NIR-PDT procedure suggested in this study with the synergistic effect of Au NE and ZnPcS could be a secure promising modality in the treatment of deep-seated tumors. Carefully increasing the power density and ambient temperature, to the extent of skin tolerance threshold value, seems to be efficient in the treatment of Hela cells.

Superparamagnetic cobalt ferrite nanoparticles as T2 contrast agent in MRI: in vitro study.

Superparamagnetic cobalt ferrite nanoparticles (CoFe2O4) possess favourite advantages for theranostic applications. Most of previous studies reported that CoFe2O4 magnetic nanoparticles (MNPs) are suitable candidates for induction of hyperthermia and transfection agents for drug delivery. The present study synthesized and investigated the potential use of CoFe2O4 as a contrast agent in magnetic resonance imaging (MRI) by using a conventional MRI system. The CoFe2O4 were synthesized using co-precipitation method and characterized by TEM, XRD, FTIR, EDX and VSM techniques. Relaxivities r1 and r2 of CoFe2O4 were then calculated using a 1.5 Tesla clinical magnetic field. The cytotoxicity of CoFe2O4 was evaluated by the MTT assay. Finally, the optimal concentrations of MNPs for MRI uses were calculated through the analysis of T2 weighted imaging cell phantoms. The superparamagnetic CoFe2O4 NPs with an average stable size of 10.45 nm were synthesized. Relaxivity r1,2 calculations resulted in suitable r2 and r2/ r1 with values of 58.6 and 51 that confirmed the size dependency on relaxivity values. The optimal concentration of MNPs for MR image acquisition was calculated as 0.154 mM. Conclusion: CoFe2O4 synthesized in this study could be considered as a suitable T2 weighted contrast agent because of its high r2/r1 value.

In-vitro investigation of cold atmospheric plasma induced photodynamic effect by Indocyanine green and Protoporphyrin IX.

BACKGROUND: Photodynamic therapy (PDT) is one of the non-invasive methods for the treatment of superficial malignant cancers. One of the limiting challenges of PDT is the hypoxic conditions during treatment that reduces PDT Efficiency. Because of ROS and free radicals in plasma flame output, Cold atmospheric plasma (CAP) may improve treatment efficiency. In this study, the effect of plasma-induced photodynamic effect of two Photosensitizers (PSs) include Indocyanine green (ICG) and Protoporphyrin IX (PPIX) on two cell lines (MCF-7 and HT-29) was investigated. METHODS: First, toxicity of different concentrations of PSs (5-50 µM) were examined on cell lines. After that, we surveyed low toxicity of PSs concentrations with different plasma radiation doses. To quantitative of cell survival, MTT assay was performed after 48 h. Finally, in order to statistical analysis of data, we used SPSS software (version 20) and also in order to better comparison the results, we used indexes such as Plasma sensitivity index and Synergism index. RESULTS: The results indicate that in most irradiant conditions; for ICG + CAP group, PSI > 1 and SI < 1 in the both of cell line (P < 0.05). Also for PPIX + CAP group in most irradiant conditions, only in the HT-29 cell line can it be said with certainty that both indexes (PSI and SI) are higher than 1 (P < 0-05). CONCLUSION: The results show that the plasma-induced photodynamic therapy with ICG and PPIX has more effective results on MCF-7 (breast cancer) and HT-29 (colon cancer) cell line, respectively. Also, the synergistic effect was observed only for PPIX in the HT-29 cell line.

Investigation of the emission spectra and cytotoxicity of TiO2 and Ti-MSN/PpIX nanoparticles to induce photodynamic effects using X-ray.

BACKGROUND: Photodynamic therapy (PDT) has been recognized as an effective method for cancer treatment; however, it suffers from limited tissue penetration depth. X-rays are ideal excitation sources for activating self-lighting nanoparticles that can penetrate through deep tumor tissues and convert the X-rays to visible light. In this study, Ti-MSN/PpIX nanoparticles for X-ray induced photodynamic therapy was synthesized. Preparation, characterization, and emission spectrum of Ti-MSN/PpIX nanoparticles as well as PDT activity and toxicity of the nanoparticles on HT-29 cell line were investigated. METHODS: Firstly, mesoporous silica nanoparticles (MSN) were synthesized through sol-gel method. Then, TiO2 and PpIX were loaded in MSN. Next, the emission spectra of TiO2, Ti-MSN, and Ti-MSN/PpIX nanoparticles, while activated by X-ray (6 MVp), were recorded. In addition, viability of cells after treatment by Ti-MSN/PpIX nanoparticles and X-ray irradiation was studied. RESULTS: SEM, TEM and FESEM images of the spherical composite nanoparticles showed that their dimensions were changed by incorporating Ti and organic compound of PpIX. Two-dimensional hexagonal structure with d100-spacing was about 3.5 nm with particle sizes of 70-110 nm. The optical characteristics of TiO2 nanoparticles showed strong emission lines, which effectively overlapped with the absorption wavelengths of protoporphyrin IX (PpIX). Cellular experiments showed Ti-MSN/PpIX nanoparticles have proper biocompatibility, however, after X-ray irradiation, significant decrease of cell viability in the presence of the nanoparticles was observed. CONCLUSION: The presented X-PDT method could enhance RT efficacy and is enable that allows for reducing X-ray dose exposure to healthy tissues to overcome radio-resistant tumors.

The Influence of Anionic, Cationic Surfactant and AOT/Water/Heptane Reverse Micelle on Photophysical Properties of Crocin: Compare with RPMI Effect.

Encapsulation of crocin (CN), having large nonlinear optical (NLO) properties, can be utilized in studies of photodynamic therapy (PDT). For this purpose, photo-physical and NLO properties of CN encapsulation with and without cell culture medium (CCM) were investigated. As well, nonlinear absorption (NLA) coefficient and nonlinear refractive (NLR) indices were found to be 10-7 (cm W-1) and 10-12 (cm2 W-1); respectively. The results revealed that NLO properties of CN had changed through its dipole moment. Reflecting on the theory of Bilot and Kawski, it was evidenced that the dipole moment of CN could change with a nano-droplet size. Furthermore, it was demonstrated that RPMI-1640 as a growth medium had failed to change NLO properties of CN encapsulated in nano-droplet. Accordingly, the encapsulated CN in nano-droplet in the form of a photosensitizer (PS) was suggested as a good candidate to examine PDT under in-vitro conditions.