Plasmonic photothermal therapy in the near-IR region using gold nanostars.

Photothermal therapy using nanoparticles is a prominent technique for cancer treatment. The principle is to maximize the heat conversion efficiency using plasmonic nanoparticle-light interaction. Due to their unique optical characteristics derived from their anisotropic structure, gold nanostars (GNSs) have gotten significant attention in photothermal therapy. To design a proper cancer treatment, it is vital to study the thermal effect induced close to the gold nanoparticles, in the vicinity, and the cancerous tissue. A temperature-dependent 2D model based on finite element method models is commonly used to simulate near-IR tumor ablation. The bioheat equation describes the photothermal effect within the GNSs and the environment. Surface cooling and heating strategies, such as the periodical heating method and a reduced laser irradiation area, were investigated to address surface overheating problems. We also determined that the optimal laser radius depends on tumor aspect ratio and laser intensity. Our results provide guidelines to evaluate a safe and feasible temperature range, treatment time, optimal laser intensity, and laser radius to annihilate a tumor volume.

Synergistic effects of combined therapy with transcranial photobiomodulation and enriched environment on depressive- and anxiety-like behaviors in a mice model of noise stress.

The development of anxiety and depression due to chronic exposure to noise stress has remained as an unsolved health problem so far. Despite the studies suggesting the neuroenhancement effects of transcranial photobiomodulation (tPBM) and housing in an enriched environment (EE), the combined effects of these treatments have not been elucidated yet. Also, there is no available data on the relationship between the application of tPBM and hippocampal brain-derived neurotrophic factor (BDNF) expression in animal models of stress. The present study aims to investigate the application of the tPBM and EE (alone or in combination) on depressive- and anxiety-like behaviors in a mice model of noise stress. Mice were divided into five groups: control, noise, noise + EE, noise + tPBM, and noise + EE + tPBM. Except for the control group, other groups were subjected to 110 dB SPL white noise for 4 h/day for 14 consecutive days and received their respective treatments. Forced Swimming Test (FST) was used to evaluate depressive-like behaviors. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. BDNF, tyrosine receptor kinase B (TrkB), and cAMP response element-binding (CREB) protein levels in the hippocampus were determined by the Western blot method, and also serum corticosterone levels were assessed using an ELISA kit. Exposure to noise stress significantly elevated serum corticosterone level; downregulated hippocampal BDNF, TrkB, and CREB protein expressions; and resulted in depressive- and anxiety-like behaviors. While, the application of tPBM (810 nm wavelength, 8 J/cm2 fluence, 10 Hz pulsed wave mode), housing in EE, and their combination lowered corticosterone levels, upregulated the BDNF/TrkB/CREB signaling pathway in the hippocampus, and improved behavioral outcomes in noise stress subjected mice. Our finding revealed the improving effects of tPBM and EE on depressive and anxiety-like behaviors induced by noise stress, possibly by augmenting the BDNF/TrkB/CREB signaling pathway.

Exact location of sensorimotor cortex injury after photochemical modulation; evidence of stroke based on stereological and morphometric studies in mice.

The integrity of the structural cerebral cortex is disrupted after stroke either at the macroscopic or microscopic levels. Therefore, many attempts have been gathered to circumvent stroke-associated problems in the brain tissue. The current study was aimed to design an animal model of photochemical stroke using rose bengal (RB) plus laser irradiation (L) after 10, 15, and 20 min (´) and evaluate its effect on the cerebral tissue using unbiased stereological quantitative methods and morphometric histological analysis. Photochemical stroke was induced by intraperitoneal injection of RB dye and further activation through the exposure of the right sensorimotor cortex with the green laser radiation (100 mW; 532 nm). Mice were randomly allocated into 4 groups (each in 15) as follows: control (10 µg/gbw RB), RB + 10'L, RB + 15'L, and RB + 20'L. Target irradiation site was adjusted to 2 mm lateral to the bregma. Vernier caliper morphometric evaluation, cresyl violet staining, and unbiased stereological assays including Cavalier's principle and point counting techniques were used to monitor the pathological changes and lesion volume on days 1, 3, and 7 after the ischemia induction. Our data showed that the mean diameter of the lesion site and lesion infarct volume in the group RB + 20'L) was significantly increased relative to the other groups (P < 0.05). Notably, the lesion volume and diameter in the group RB + 15'L was larger compared with the group RB + 10'L and control mice (P < 0.05). Data showed an increased acute inflammatory response such as hyperemia and edema 3 days after ischemic induction while the intensity of acute changes and lesion volume were reduced and replaced with necrotic and chronic pathological changes including astrogliosis on day 7. It is concluded that the laser irradiation of RB-injected mice at a distinct time period could induce the magnificent degenerative effects on the cerebral cortex which is similar to the stroke condition.

Effects of transcranial photobiomodulation and methylene blue on biochemical and behavioral profiles in mice stress model.

The effectiveness of transcranial photobiomodulation (tPBM) and methylene Blue (MB) in treating learning and memory impairments is previously reported. In this study, we investigated the effect of tPBM and MB in combination or alone on unpredictable chronic mild stress (UCMS)-induced learning and memory impairments in mice. Fifty-five male BALB/c mice were randomly allocated to five groups: control, laser sham + normal saline (NS), tPBM + NS, laser sham + MB, and tPBM + MB. All groups except the control underwent UCMS and were treated simultaneously for 4 weeks. Elevated plus maze (EPM) was used to evaluate anxiety-like behaviors. Novel object recognition (NOR) test and Barnes maze tests were used to evaluate learning and memory function. The serum cortisol and brain nitric oxide (NO), reactive oxygen species (ROS), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels were measured by spectrophotometric methods. Behavioral tests revealed that UCMS impaired learning and memory, and treatment with PBM, MB, and their combination reversed these impairments. Levels of NO, ROS, SOD activity in brain, and serum cortisol levels significantly increased while brain GPx activity and total antioxidant capacity significantly decreased in the sham + NS animals when compared with the controls. A significant improvement was observed in treatment groups due to reversion of the aforementioned molecular analysis caused by UCMS when it was compared with control levels. Both tPBM and MB in combination or alone have significant therapeutic effects on learning and memory impairments in UCMS-received animals.

Correction to: Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling.

After publication of this paper, the authors determined an error in Fig. 4. Below is the correct Fig. 4.

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser.

OBJECTIVES: The effectiveness of transcranial photobiomodulation (TPBM) in treating anxiety and depression disorders is a demonstrated and identified issue. However, the optimum therapeutic dose and the underlying mechanism of action are not fully understood. In this study, the therapeutic effects of three different near-infrared (NIR) doses on anxiety- and depression-like behaviors as well as cerebral levels of serotonin (5-HT) and nitric oxide (NO) were evaluated in a mouse model of chronic restraint stress (CRS). MATERIALS AND METHODS: CRS procedure (3 hours/day, over 3 weeks) was performed as a typical stress model to study anxiety and depression along with laser treatment (3 times/week, over 3 weeks), which began simultaneously with CRS. A NIR diode laser (810 nm wavelength, 10 Hz) with the output power of 200 mW and power density of 4.75 W/cm2 was implemented to deliver three different doses of 4, 8, and 16 J/cm2 to the cerebral cortex of mice. Behavioral experiments including open field, tail suspension, and elevated plus maze tests as well as serum cortisol levels were assessed to evaluate the anti-anxiety and anti-depressive effects of NIR TPBM. The changes of 5-HT and NO levels in the prefrontal cortex (PFC) and hippocampus (Hipp) were assessed. RESULTS: CRS procedure induced anxiety- and depression-like behaviors, increased serum cortisol levels, decreased 5-HT and increased NO levels in the PFC and Hipp areas. NIR TPBM improved behavioral results, decreased serum cortisol levels, increased 5-HT and decreased NO concentrations in the PFC and Hipp. A dose of 8 J/cm2 of NIR TPBM showed the maximum effects on behavioral and molecular results, while a decline was observed from the optimum effects at both lower (4 J/cm2 ) and higher (16 J/cm2 ) doses. CONCLUSION: Our results demonstrated that NIR TPBM had an anti-anxiety and anti-depressive effect in CRS mice, which is probably linked to increasing 5-HT and decreasing NO levels in the PFC and Hipp areas. Also, the maximum anti-anxiety and anti-depressive effect was produced at dose of 8 J/cm2 . Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling.

The distinct role of low-level laser irradiation (LLLI) on endothelial exosome biogenesis remains unclear. We hypothesize that laser irradiation of high dose in human endothelial cells (ECs) contributes to the modulation of exosome biogenesis via Wnt signaling pathway. When human ECs were treated with LLLI at a power density of 80 J/cm2, the survival rate reduced. The potential of irradiated cells to release exosomes was increased significantly by expressing genes CD63, Alix, Rab27a, and b. This occurrence coincided with an enhanced acetylcholine esterase activity, pseudopodia formation, and reduced zeta potential value 24 h post-irradiation. Western blotting showed the induction of LC3 and reduced level of P62, confirming autophagy response. Flow cytometry and electron microscopy analyses revealed the health status of the mitochondrial function indicated by normal ΔΨ activity without any changes in the transcription level of PINK1 and Optineurin. When cells exposed to high power laser irradiation, p-Akt/Akt ratio and in vitro tubulogenesis capacity were blunted. PCR array and bioinformatics analyses showed the induction of transcription factors promoting Wnt signaling pathways and GTPase activity. Thus, LLLI at high power intensity increased exosome biogenesis by the induction of autophagy and Wnt signaling. LLLI at high power intensity increases exosome biogenesis by engaging the transcription factors related to Wnt signaling and autophagy stimulate.

How do red and infrared low-level lasers affect folliculogenesis cycle in rat's ovary tissue in comparison with clomiphene under in vivo condition.

Folliculogenesis is a cycle that produces the majority of oocyte. Any disruption to this cycle leads to ovulation diseases, like polycystic ovarian syndrome (PCOS). Treatments include drugs and surgery; lasers have also been used complementarily. Meanwhile, still there is no definite treatment for PCOS. This study investigated the photo-bio stimulation effect of near-infrared and red low-level laser on producing follicles and compared the result with result of using common drug, clomiphene. Therefore, the aim of this study was to propose the use of lasers autonomously treatment. So, there was one question: how do lasers affect folliculogenesis cycle in rat's ovary tissue? In this study, 28 rats were assigned to four groups as follows: control (CT), clomiphene drug (D), red laser (RL), and near-infrared laser (NIRL). Afterwards, 14 rats of RL and NIRL groups received laser on the first 2 days of estrous cycle, each 6 days, for 48 days. During treatment period, each rat received energy density of 5 J/cm2. Seven rats in D group received clomiphene. After the experiment, lasers' effects at two wavelengths of 630 and 810 nm groups have been investigated and compared with clomiphene and CT groups. Producing different follicles to complement folliculogenesis cycle increased in NIRL and RL groups, but this increase was significant only in the NIRL group. This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS.

Therapeutic effects of 10-HzPulsed wave lasers in rat depression model: A comparison between near-infrared and red wavelengths.

BACKGROUND AND OBJECTIVE: The application of transcranial low-level light/laser therapy (tLLLT) in the range of red to near-infrared (NIR) spectrum for psychological disorders is a new area that is attracting growing interest in recent years. The photomodulation effects of NIR and red coherent lights on the activity of cytochrome c oxidase in neuronal cells of brain have been recently introduced. This study, therefore, sought to compare the therapeutic effects of 10-Hz pulsed wave NIR (810 nm) laser with red (630 nm) laser using the same delivered energy density and Citalopram in rat chronic mild stress (CMS) model of depression and anxiety. MATERIALS AND METHODS: CMS procedures (for 4 weeks) were used to induce stress. GaAlAs diode laser with red and NIR wavelengths on 10-Hz pulsed wave (50% duty cycle) were used to perform tLLLT treatment for three weeks. An energy density of about 1.2 J/cm-(2) per each session was delivered through a light spot with a diameter of 3-mm to the prefrontal cortex for both wavelengths. Citalopram (10 mg/kg, Intraperitoneal) was administered for twenty-one consecutive days to the drug group. RESULTS: The findings of the present study showed an increase in swimming and decrease in immobility time, for both NIR laser and Citalopram groups compared to the stress group in forced swimming test. Anxiety-like behaviors showed insignificant decrease in all treatment groups in elevated plus maze test. The induction of stress significantly increased serum cortisol levels and treatments with both red laser and Citalopram decreased it. Hyperglycemia induced by CMS returned to normal levels in all treatment groups. The assessment of body weight also showed a significant increase in NIR laser group compared to the stress group by the end of the experiment. CONCLUSIONS: This study showed that non-invasive tLLLT using 10-Hz pulsed NIR laser light was as effective as Citalopram and more effective than red laser in the treatment of depressive-like behaviors and may help improve tLLLT as an alternative non-pharmacological treatments of psychological disorders such as depression. Lasers Surg. Med. 48:695-705, 2016. © 2016 Wiley Periodicals, Inc.

Automatic Choroidal Segmentation in Optical Coherence Tomography Images Based on Curvelet Transform and Graph Theory.

Background: Automatic segmentation of the choroid on optical coherence tomography (OCT) images helps ophthalmologists in diagnosing eye pathologies. Compared to manual segmentations, it is faster and is not affected by human errors. The presence of the large speckle noise in the OCT images limits the automatic segmentation and interpretation of them. To solve this problem, a new curvelet transform-based K-SVD method is proposed in this study. Furthermore, the dataset was manually segmented by a retinal ophthalmologist to draw a comparison with the proposed automatic segmentation technique. Methods: In this study, curvelet transform-based K-SVD dictionary learning and Lucy-Richardson algorithm were used to remove the speckle noise from OCT images. The Outer/Inner Choroidal Boundaries (O/ICB) were determined utilizing graph theory. The area between ICB and outer choroidal boundary was considered as the choroidal region. Results: The proposed method was evaluated on our dataset and the average dice similarity coefficient (DSC) was calculated to be 92.14% ± 3.30% between automatic and manual segmented regions. Moreover, by applying the latest presented open-source algorithm by Mazzaferri et al. on our dataset, the mean DSC was calculated to be 55.75% ± 14.54%. Conclusions: A significant similarity was observed between automatic and manual segmentations. Automatic segmentation of the choroidal layer could be also utilized in large-scale quantitative studies of the choroid.

An Update on Choroidal Layer Segmentation Methods in Optical Coherence Tomography Images: a Review.

Choroid is one of the structural layers, playing a significant role in physiology of the eye and lying between the sclera and the retina. The segmentation of this layer could guide ophthalmologists in diagnosing most of the eye pathologies such as choroidal tumors and polypoidal choroidal vasculopathy. High signal-to-noise ratio and high speed imaging in Spectral-Domain Optical Coherence Tomography (SD-OCT) make choroidal imaging feasible. Several variables such as pre-operative axial length (AXL), time of day and age affect thickness of the choroidal vascularization and should be considered for segmentation of this layer. These days most of the eye specialists manually segment the choroidal layer which is time-consuming, tiresome and dependent on human errors. To overcome these difficulties, some studies have introduced different automatic choroidal segmentation methods. In this paper, we have conducted a comprehensive review on existing recently published methods for automatic choroidal segmentation algorithms.

Neural activity in self-identified claustrophobic individuals under in-vivo stimuli: A human electroencephalography dataset.

The electrocortical activity in claustrophobic situations is a very limited field of study and has recently caught researchers' attention. This article represents a set of electroencephalographic (EEG) data obtained from twenty-two participants. The volunteers include 9 participants with self-identified claustrophobia and 13 healthy controls under in-vivo stimuli. The EEG data were recorded using Mitsar 31-channel EEG system. Before cortical signal recording, Individuals were asked to identify themselves as healthy controls or claustrophobic participants. The EEG data collection process consisted of three experimental conditions. In all conditions, the participants were asked to stay calm and keep their eyes open. The first experimental condition was at seated resting state in a relatively large and well-lit laboratory (8m × 15m) area. In the second experimental condition, the subjects entered a moderately-lit chamber and repeated the previous resting situation. The final condition of the EEG data acquisition was performed in the same chamber but with reduced dimensions. For each experimental condition, duration of data collection was approximately 300 s. This data can be used to understand the brain's response in claustrophobic situations through various statistical or data-driven methods.

Automatic classification of schizophrenia patients using resting-state EEG signals.

Schizophrenia is one of the serious mental disorders, which can suspend the patient from all aspects of life. In this paper we introduced a new method based on the adaptive neuro fuzzy inference system (ANFIS) to classify recorded electroencephalogram (EEG) signals from 14 schizophrenia patients and 14 age-matched control participants. Sixteen EEG channels from 19 main channels that had the most discriminatory information were selected. Possible artifacts of these channels were eliminated with the second-order Butterworth filter. Four features, Shannon entropy, spectral entropy, approximate entropy, and the absolute value of the highest slope of autoregressive coefficients (AVLSAC) were extracted from each selected EEG channel in 5 frequency sub-bands, Delta, Theta, Alpha, Beta, and Gamma. Forty-six features were introduced among the 640 possible ones, and the results included accuracies of near 100%, 98.89%, and 95.59% for classifiers of ANFIS, support vector machine (SVM), and artificial neural network (ANN), respectively. Also, our results show that channels of alpha of O1, theta and delta of Fz and F8, and gamma of Fp1 have the most discriminatory information between the two groups. The performance of our proposed model was also compared with the recently published approaches. This study led to presenting a new decision support system (DSS) that can receive a person's EEG signal and separates the schizophrenia patient and healthy subjects with high accuracy.

Electroencephalographic Activity in Patients with Claustrophobia: A Pilot Study.

BACKGROUND: Exposure to small confined spaces evokes physiological responses such as increased heart rate in claustrophobic patients. However, little is known about electrocortical activity while these people are functionally exposed to such phobic situations. The aim of this study was to examine possible changes in electrocortical activity in this population. METHOD: Two highly affected patients with claustrophobia and two healthy controls participated in this in vivo study during which electroencephalographic (EEG) activity was continuously recorded. Relative power spectral density (rPSD) was compared between two situations of being relaxed in a well-lit open area, and sitting in a relaxed chair in a small (90 cm × 180 cm × 155 cm) chamber with a dim light. This comparison of rPSDs in five frequency bands of EEG was intended to investigate possible patterns of change in electrical activity during fear-related situation. This possible change was also compared between claustrophobic patients and healthy controls in all cortical areas. RESULTS: Statistical models showed that there is a significant interaction between groups of participants and experimental situations in all frequency bands (P < 0.01). In other words, claustrophobic patients showed significantly different changes in electrical activity while going from rest to the test situation. Clear differences were observed in alpha and theta bands. In the theta band, while healthy controls showed an increase in rPSD, claustrophobic patients showed an opposite decrease in the power of electrical activity when entering the confined chamber. In alpha band, both groups showed an increase in rPSD, though this increase was significantly higher for claustrophobic patients. CONCLUSION: The effect of in vivo exposure to confined environments on EEG activity is different in claustrophobic patients than in healthy controls. Most of this contrast is observed in central and parietal areas of the cortex, and in the alpha and theta bands.

Trend in creatinine determining methods: Conventional methods to molecular-based methods.

Renal failure (RF) disease is ranked as one of the most prevalent diseases with severe morbidity and mortality. Early diagnosis of RF leads to subsequent control of disease to reduce the poor prognosis. The level of sera creatinine is considered as a significant biomarker for kidney biofunction, which is routinely detected by the Jaffe reaction. The normal range for creatinine in the blood may be 0.84-1.21 mg/dL. Low accuracy, insufficient sensitivity, explosive and toxicity of picric acid, and pseudo-interaction with nonspecific elements such as ammonium ions in the Jaffe method lead to the development of various techniques for precise detection of creatinine such as spectroscopic, electrochemical, and chromatography approaches and sensors based on enzymes, molecular imprinted polymer and nanoparticles, etc. Based on previously established results, they are trying to construct sensors with high accuracy, optimum sensitivity, acceptable linear/calibration range, and limit of detection, which are small in size and applicable by the patient him/herself (point-of-care testing). By comparing the results of research, a molecularly imprinted electrochemiluminescence-based sensor with linear/calibration range of 5-1 mMconcentration of creatinine and the detection limit of 0.5 nM has the best detectable resolution with 2 million measurable points. In this paper, we will review the recently developed methods for measuring creatinine concentration and renal biofunction.

An optimal method for measuring biomarkers: colorimetric optical image processing for determination of creatinine concentration using silver nanoparticles.

Creatinine concentration is one of the important elements in the body for diagnosing kidney failure, muscular dystrophy, glomerular filtration rate, and diabetic nephropathy. The disadvantages of recently introduced analytical techniques, such as Jaffe's, spectroscopic, colorimetric, and chromatographic methods, for quantifying creatinine in urine involve toxicity, the high cost, interference, and the complexity of the design. In this paper, we designed and fabricated a new colorimetric assay for the measurement of creatinine concentration based on color differentiation generated by mixing different concentrations of creatinine with synthesized silver nanoparticles (AgNPs) coated with polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). An isolated box is designed for the uniform optical imaging of solutions, the captured images are processed in real time, and the quantitative and qualitative results are displayed. For colorimetric processing, a variety of color systems, such as RGB (red, green, blue), CMYK (cyan, magenta, yellow, black), and grayscale (Gr), have been evaluated, indicating that the combination of green (G) and grayscale (Gr) provides the best results for this experiment. TEM analysis and spectroscopy were used to confirm the results of the experiment. Linear range and limit of detection (LOD) were obtained for AgNPs/PVP 0.03-1 mg/dl and 0.024 mg/dl and for AgNPs/PVA 0.01-1 mg/dl and 0.014 mg/dl, respectively, indicating the superiority of our proposed method over recently introduced methods. In this experiment, the detectable resolution with AgNPs/PVP is 40, while it is 71 with AgNPs/PVA. The designed system is simple to use, small in size, and cost-effective for measuring creatinine concentration, while it can be used as a portable system.

Hyaluronic Acid and Regenerative Medicine: New Insights into the Stroke Therapy.

Stroke is known as one of the very important public health problems that are related to societal burden and tremendous economic losses. It has been shown that there are few therapeutic approaches for the treatment of this disease. In this regard, the present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neuro recovery. Among these therapies, regenerative medicine-based therapies have appeared as new ways of stroke therapy. Hyaluronic acid (HA) is a new candidate, which could be applied as a regenerative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan composed of disaccharide repeating elements (N-acetyl-Dglucosamine and D-glucuronic acid). Multiple lines of evidence demonstrated that HA has critical roles in normal tissues. It can be a key player in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of the extracellular matrix. HA has very important physicochemical properties i.e., availability of reactive functional groups and its solubility, which make it a biocompatible material for application in regenerative medicine. Given that HAbased bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic, they are used as soft tissue fillers and injectable dermal fillers. Several studies indicated that HA could be employed as a new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacological effects via affecting stroke-related processes. Herein, we summarized the role of the extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies for the treatment of stroke.

Novel Chemo-Photothermal Therapy in Breast Cancer Using Methotrexate-Loaded Folic Acid Conjugated Au@SiO2 Nanoparticles.

Low level laser therapy (LLLT) is known as a safe type of phototherapy to target tumor tissue/cells. Besides, using targeted nanoparticles increases the successfulness of cancer therapy. This study was designed for investigating the combined effect of folate (FA)/Methotrexate (MTX) loaded silica coated gold (Au@SiO2) nanoparticles (NPs) and LLLT on the fight against breast cancer.NPs were synthesized and characterized using FTIR, TEM and DLS-Zeta. The NPs had spherical morphology with mean diameter of around 25 nm and positive charge (+13.3 mV) while after conjugation with FA and MTX their net charge reduced to around -19.7 mV.Our findings in cell uptake studies clearly showed enhanced cellular uptake of NPs after FA and MTX loaded NPs in both breast cancer cell lines especially on MDA-MB-231 due to high expression of folate receptors. The results indicated that LLLT had a proliferative effect on both breast cancer cell lines but in the presence of engineered breast cancer targeted nanoparticle, the efficacy of combination chemo-photothermal therapy was significantly increased using MTT assay (p<0.05), DAPI staining, and cell cycle findings. The highest apoptotic effect on breast cancer cell lines was observed in the cells exposed to a combination of MTX-FA loaded Au@SiO2 NP and LLLT proved by DAPI staining and cell cycle(by increasing the cell arrest in subG0/G1). Taken together a combination of chemotherapy and LLLT improves the potential of breast cancer therapy with minimum side effects.

Low-Level Laser Irradiation Modulated Viability of Normal and Tumor Human Lymphocytes In Vitro.

Introduction: Laser radiation is a promising strategy against various malignancies. Recent studies have shown that the application of low-power laser therapy (LPLT) at different doses and exposure times could modulate the growth dynamic of tumor cells. Based on the type of laser, LPLT could potentially trigger cell proliferation, differentiation, and apoptosis in different cell lines. Methods: In this study, MTT assay was used to monitor the effect of low and high laser intensities on the viability of normal and cancer lymphocytes. The protein levels of Ki-67 (a proliferation marker) and Caspase-3 (an apoptosis factor) were measured in human peripheral mononuclear cells (PBMCs) and the B-lymphoblastic cell line (Nalm-6) using flow cytometry after being-exposed to 630-nm LPLT at low (2, 4, 6, and 10 J/cm2 ) and high (15, 30, 60, and 120 J/cm2) energy densities in a continuous mode for 48 and 72 hours. Results: By using higher energy densities, 60 and 120 J/cm2 , a significant decrease was shown in the viability of Nalm-6 cells, which reached 6.6 and 10.1% after 48 hours compared to the control cells (P<0.05). Notably, Cell exposure to doses 30, 60, and 120 J/cm2 yielded 7.5, 12.9, and 21.6 cell viability reduction after 72 hours. The collected data showed that the high-intensity parameters of LPLT (15 to 120 J/cm2) promoted significant apoptotic changes in the exposed cells coincided with the activation of Caspase-3 compared to the none-treated control cells (P<0.05). The data further showed the stimulation of the Ki-67 factor both in primary PBMCs and the lymphoblastic cell line treated with LPLT at energy densities of 4 and 6 J/cm2 (P<0.05), indicating enhanced cell proliferation. Similar to Nalm-6 cells, primary PBMCs showed apoptosis after 48 hours of being exposed to doses 60, and 120 J/cm2 , indicated by increased Caspase-3 levels (P<0.05). As expected, the Nalm-6 cells were resistant to cytotoxic effects of laser irradiation in the first 48 hours (P>0.05) compared to normal PBMCs. The exposure of Nalm-6 cells to low-intensity laser intensities increased a proliferation rate compared to the PBMCs treated with the same doses. Conclusion: We showed the potency of LPLT in the induction of apoptosis and proliferation in human primary PBMCs and Nalm-6 cells in a dose and time-dependent manner after 72 hours.

A simple strategy for chemo-photothermal ablation of breast cancer cells by novel smart gold nanoparticles.

Combined therapeutics dependent on the synergistic effect between photothermal therapy (PTT) and chemotherapy have been anticipated to be the next generation of cancer treatment. For this purpose, a novel gold hydrosol was synthesized by a one-pot approach using poly (2-(dimethylamino) ethyl methacrylate-co- N-isopropylacrylamide-co- 2-vinylpyridine) P(DMAEMA-co-NIPAAM-co-VP) terpolymers as a reducing and stabilizing agent. The synthesized gold hydrosol was recoated by a novel carboxylic acid rich poly (N-isopropyl acrylamide-co-maleic anhydride-graft-citric acid) (PNIPAAm-co-PMA-g-CA) copolymer. Then the gold nanoparticles conjugated with Doxorubicin (DOX) and served as a smart photo synthesizer for chemo/photothermal therapy of MCF-7 breast cancer cells. The synthesized nanoparticles had mono-dispersed spherical morphology with a diameter below 30 nm. Our results from cellular uptake indicated that around 100% of the particles were uptake by MCF-7 cells in the first 3 h of exposure time. The temperature of nanocomposites considerably went up to 45 °C with 10 min exposure to near-infrared irradiation. As a striking result, a single round of PTT combined with a sub-therapeutic dose of DOX revealed a synergistic effect with an ability of robust anti-tumor response up to 99.99% (sum of the population of apoptotic and necrotic cells) demonstrated by Annexin-V, cell cycle and DAPI staining techniques. In conclusion, Near-infrared-mediated photothermal conversion exhibited high effectiveness of a combinational chemo-thermotherapy to treat cancer cells.