New insights into targeted therapy of glioblastoma using smart nanoparticles.

In recent times, the intersection of nanotechnology and biomedical research has given rise to nanobiomedicine, a captivating realm that holds immense promise for revolutionizing diagnostic and therapeutic approaches in the field of cancer. This innovative fusion of biology, medicine, and nanotechnology aims to create diagnostic and therapeutic agents with enhanced safety and efficacy, particularly in the realm of theranostics for various malignancies. Diverse inorganic, organic, and hybrid organic-inorganic nanoparticles, each possessing unique properties, have been introduced into this domain. This review seeks to highlight the latest strides in targeted glioblastoma therapy by focusing on the application of inorganic smart nanoparticles. Beyond exploring the general role of nanotechnology in medical applications, this review delves into groundbreaking strategies for glioblastoma treatment, showcasing the potential of smart nanoparticles through in vitro studies, in vivo investigations, and ongoing clinical trials.

3D modeling of in vivo MRI-guided nano-photothermal therapy mediated by magneto-plasmonic nanohybrids.

BACKGROUND: Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. METHODS: This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) files of mice bodies and nanohybrid distribution in the tumor were established to create a realistic geometry for the model. The accuracy of the temperature predictions was validated by using an infrared (IR) camera. RESULTS: The photothermal conversion efficiency of the nanohybrids was experimentally determined to be approximately 30%. The intratumoral (IT) injection group showed the highest temperature increase, with a maximum of 17 °C observed at the hottest point on the surface of the tumor-bearing mice for 300 s of laser exposure at a power density of 1.4 W/cm2. Furthermore, the highest level of tissue damage, with a maximum value of Ω = 0.4, was observed in the IT injection group, as determined through a simulation study. CONCLUSIONS: Our synthesized nanohybrid shows potential as an effective agent for MRI-guided NPTT. The developed model accurately predicted temperature distributions and tissue damage in the tumor. However, the current temperature validation method, which relies on limited 2D measurements, may be too lenient. Further refinement is necessary to improve validation. Nevertheless, the presented FEM model holds great promise for clinical NPTT treatment planning.

SARS-CoV-2 and influenza viruses: Strategies to cope with coinfection and bioinformatics perspective.

Almost a century after the devastating pandemic of the Spanish flu, humankind is facing the relatively comparable global outbreak of COVID-19. COVID-19 is an infectious disease caused by SARS-CoV-2 with an unprecedented transmission pattern. In the face of the recent repercussions of COVID-19, many have argued that the clinical experience with influenza through the last century may have tremendous implications in the containment of this newly emerged viral disease. During the last 2 years, from the emergence of COVID-19, tremendous advances have been made in diagnosing and treating coinfections. Several approved vaccines are available now for the primary prevention of COVID-19 and specific treatments exist to alleviate symptoms. The present review article aims to discuss the pathophysiology, diagnosis, and treatment of SARS-CoV-2 and influenza A virus coinfection while delivering a bioinformatics-based insight into this subject matter.

Convalescent Blood: Current Perspective on the Efficacy of a Legacy Approach in COVID-19 Treatment.

Since early 2020, COVID-19 has wreaked havoc in many societies around the world. As of the present, the SARS-CoV-2-borne disease is propagating in almost all countries, affecting hundreds of thousands of people in an unprecedented way. As the name suggests, the novel coronavirus, widely known as SARS-CoV-2, is a new emerging human pathogen. A novel disease of relatively unknown origin, COVID-19 does not seem to be amenable to the currently available medicines since there is no specific cure for the disease. In the absence of any vaccine or effective antiviral medication, we have no tools at our disposal, but the method of quarantine, be it domestic or institutional, to hinder any further progression of this outbreak. However, there is a record of physicians in the past who practiced convalescent blood transfusion. To their awe, the method seemed to be useful. It is anticipated that these contemporary methods will outdo any other vaccination process in the time being, as blood transfusion is instead a cost-effective and time-friendly technique. Following a successful trial, this new approach of contemporary nature to a viral disease may serve as an emergency intervention to intercept infectious outbreaks and prevent an impending epidemic/pandemic. In this review, we document the most recent evidence regarding the efficiency of convalescent plasma and serum therapy on SARS, MERS, and particularly COVID-19, while discussing potential advantages and possible risks of such practice.

Monitoring of the choline/lipid ratio by 1H-MRS can be helpful for prediction and early detection of tumor response to nano-photo-thermal therapy.

Nanotechnology-based photothermal therapy (NPTT) is a new emerging modality of cancer therapy. To have the right prediction and early detection of response to NPTT, it is necessary to get rapid feedback from a tumor treated by NPTT procedure and stay informed of what happens in the tumor site. We performed this study to find if proton magnetic resonance spectroscopy (1H-MRS) can be well responsive to such an imperative requirement. We considered various treatment groups including gold nanoparticles (AuNPs), laser, and the combination of AuNPs and laser (NPTT group). Therapeutic effects on CT26 colon tumor-bearing BALB/c mice were studied by looking at alterations that happened in 1H-MRS signals and tumor size after conducting treatment procedures. In MRS studies, the alterations of choline and lipid concentrations and their ratio were investigated. Having normalized the metabolite peak to water peak, we found a significant decrease in choline concentration post-NPTT (from (1.25 ± 0.05) × 10-3 to (0.43 ± 0.04) × 10-3), while the level of lipid concentration in the tumor was slightly increased (from (2.91 ± 0.23) × 10-3 to (3.52 ± 0.31) × 10-3). As a result, the choline/lipid ratio was significantly decreased post-NPTT (from 0.41 ± 0.11 to 0.11 ± 0.02). Such alterations appeared just 1 day after NPTT. Tumor shrinkage in all groups was studied and significant changes were significantly detectable on day 7 post-NPTT procedure. In conclusion, the study of choline/lipid ratio using 1H-MRS may help us estimate what happens in a tumor treated by the NPTT method. Such an in vivo assessment is interestingly feasible as soon as just 1 day post-NPTT. This would undoubtedly help the oncologists make a more precise decision about treatment planning strategies. Monitoring of the choline/lipid ratio by 1H-MRS can be helpful for prediction and early detection of response to nano-photo-thermal therapy.

Short-term celecoxib (celebrex) adjuvant therapy: a clinical trial study on COVID-19 patients.

BACKGROUND: It is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current documents have demonstrated that the virus causes a PGE2 storm in a substantial proportion of patients via upregulating cyclooxygenase-2 (COX-2) and downregulating prostaglandin E2 (PGE2)-degrading enzymes within the host cell. AIM: Herein, we aimed to study how short-term treatment with celecoxib (Celebrex), a selective COX-2 inhibitor, affects demographic features, early symptoms, O2 saturation, and hematological indices of cases with COVID-19. METHODS: A total of 67 confirmed COVID-19 cases with a mild or moderate disease, who had been referred to an institutional hospital in south-eastern Iran from October 2020 to September 2021, were enrolled. Demographic characteristics, symptoms, and hematological indices of the patients were recorded within different time periods. One-way ANOVA or Kruskal-Wallis tests were used to determine differences between data sets based on normal data distribution. RESULTS: O2 saturation was statistically different between the control group and patients receiving celecoxib (p = 0.039). There was no marked difference between the groups in terms of the symptoms they experienced (p > 0.05). On the first days following Celebrex therapy, analysis of complete blood counts showed that white blood cell (WBC) counts were markedly lower in patients treated with a high dose of celecoxib (0.4 g/day) than in controls (p = 0.026). However, mean lymphocyte levels in patients receiving a high dose of celecoxib (0.4 g/day) were markedly higher than in patients receiving celecoxib with half of the dose (0.2 g/day) for one week or the untreated subjects (p = 0.004). Changes in platelet count also followed the WBC alteration pattern. CONCLUSION: Celecoxib is a relatively safe, inexpensive, and widely available drug with non-steroidal anti-inflammatory properties. The therapeutic efficacy of celecoxib depends on the administrated dose. Celecoxib might improve disease-free survival in patients with COVID-19.

An Updated Review on Implications of Autophagy and Apoptosis in Tumorigenesis: Possible Alterations in Autophagy through Engineered Nanomaterials and Their Importance in Cancer Therapy.

Most commonly recognized as a catabolic pathway, autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components, i.e., organelles, by means of certain membranous vesicles or lysosomes filled with degrading enzymes. Upon exposure to external insult or internal stimuli, the cell might opt to activate such a pathway, through which it can gain control over the maintenance of intracellular components and thus sustain homeostasis by intercepting the formation of unnecessary structures or eliminating the already present dysfunctional or inutile organelles. Despite such appropriateness, autophagy might also be considered a frailty for the cell, as it has been said to have a rather complicated role in tumorigenesis. A merit in the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. In fact, several investigations on tumorigenesis have reported diminished levels of autophagic activity in tumor cells, which might result in transition to malignancy. On the contrary, autophagy has been suggested to be a seemingly favorable mechanism to progressed malignancies, as it contributes to survival of such cells. Based on the recent literature, this mechanism might also be activated upon the entry of engineered nanomaterials inside a cell, supposedly protecting the host from foreign materials. Accordingly, there is a good chance that therapeutic interventions for modulating autophagy in malignant cells using nanoparticles may sensitize cancerous cells to certain treatment modalities, e.g., radiotherapy. In this review, we will discuss the signaling pathways involved in autophagy and the significance of the mechanism itself in apoptosis and tumorigenesis while shedding light on possible alterations in autophagy through engineered nanomaterials and their potential therapeutic applications in cancer. SIGNIFICANCE STATEMENT: Autophagy has been said to have a complicated role in tumorigenesis. In the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. On the contrary, autophagy has been suggested to be a favorable mechanism to progressed malignancies. This mechanism might be affected upon the entry of nanomaterials inside a cell. Accordingly, therapeutic interventions for modulating autophagy using nanoparticles may sensitize cancerous cells to certain therapies.

Application of Nanobiotechnology for Early Diagnosis of SARS-CoV-2 Infection in the COVID-19 Pandemic.

A most discussed topic of the new decade, COVID-19 is an infectious disease caused by the recently discovered SARS-CoV-2. With an exceedingly high transmission rate, COVID-19 has affected almost all the countries in the world. Absent any vaccine or specific treatment, the humanity is left with nothing but the legacy method of quarantine. However, quarantine can only be effective when combined with early diagnosis of suspected cases. With their high sensitivity and unmatched specificity, biosensors have become an area of interest for development of novel diagnostic methods. Compared to the more traditional diagnostics, nanobiotechnology introduces biosensors as different diagnostics with greater versatility in application. Today, a growing number of analytes are being accurately identified by these nanoscopic sensing machines. Several reports of validated application with real samples further strengthen this idea. As of recent, there has been a rise in the number of studies on portable biosensors. Despite the slow progression, certain devices with embedded biosensors have managed to be of diagnostic value in several countries. The perceptible increase in development of mobile platforms has revolutionized the healthcare delivery system in the new millennium. The present article reviews the most recent advancements in development of diagnostic nanobiosensors and their application in the clinical fields. KEY POINTS: • There is no specific treatment for highly transmissible SARS-CoV-2. • Early diagnosis is critical for control of pandemic. • Highly sensitive/specific nanobiosensors are emerging assets against COVID-19.

Cardioprotective Effects of Mebudipine in a Rat Model of Doxorubicin-Induced Heart Failure.

Background: Mebudipine, a dihydropyridine calcium-channel blocker (CCB), shows greater time- and voltage-dependent inhibitory effects than nifedipine. Its significant negative chronotropic effects without having considerable negative inotropic properties may make it a suitable candidate for the pharmacotherapy of heart failure (HF). This study aimed to investigate the possible beneficial action of mebudipine in a rat model of HF. Methods: The present study carried out in the Department of Pharmacology at the Iran University of Medical Sciences during the years of 2009-2011. An experimental model of HF was induced in male Wistar rats using doxorubicin (DOX). The rats were divided into five groups with seven animals in each group: normal control group, DOX-induced HF control groups, and treatment groups. The animals were administered DOX for 15 days. A consistent deterioration occurred after a four-week rest period. The animals were then treated with intraperitoneal mebudipine (0.5 mg/kg) and intraperitoneal amlodipine (0.35 mg/kg), as well as an equal volume of distilled water for 15 days. The plasma levels of big endothelin-1 (BET-1), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as the clinical status (heart rate and blood pressure), were assessed before and after treatment. Statistical analysis was performed with SPSS software using parametric and nonparametric ANOVA. Results: Mebudipine and amlodipine reversed the increased plasma BET-1 values in the treated animals when compared with the HF control group (0.103 and 0.112 vs 0.231 pg/mL, respectively). The increased plasma levels of AST, ALT, CK-MB, and LDH were also reversed in the HF animals that received mebudipine or amlodipine. Conclusion: The administration of mebudipine to HF animals, akin to amlodipine, palliated the clinical and biochemical signs of the disease in the present study. The abstract was presented in the Iranian Congress of Physiology and Pharmacology as a poster and published in the Scientific Information Database as a supplement (2015; Vol 22).

COVID-19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019-nCoV disease.

Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.

A binuclear iron(III) complex of 5,5'-dimethyl-2,2'-bipyridine as cytotoxic agent.

The binuclear iron(III) complex (1), namely, {[Fe(5,5'-dmbpy)2(OH2)]2(µ-O)}(NO3)4 with a distorted octahedral coordination, formed by four nitrogen and two oxygen atoms, was previously reported by our team. In this study the DNA-binding and cytotoxicity evaluation for target complex were studied. The results indicated strong cytotoxicity activity against A549 cells comparable to cisplatin values. The binding interaction between complex 1 and FS-DNA was investigated by UV-Vis, fluorescence spectroscopy, and gel electrophoresis at physiological pH (7.2). The DNA binding investigation has shown groove binding interactions with complex 1, therefore the hydrogen binding plays an important role in the interaction of DNA with complex 1. The calculated thermodynamic parameters (ΔH°, ΔS° and ΔG°) show that hydrogen bonding and Vander-Waals forces have an important function in Fe(III) complex-DNA interaction. Moreover, DNA cleavage was studied using agarose gel electrophoresis. Viscosity measurements illustrated that relative viscosity of DNA was unchanged with the adding concentrations of Fe(III) complex. Molecular docking simulation results confirmed the spectroscopic and viscosity titration outcomes.

A thermo-responsive alginate nanogel platform co-loaded with gold nanoparticles and cisplatin for combined cancer chemo-photothermal therapy.

The current interest in cancer research is being shifted from individual therapy to combinatorial therapy. In this contribution, a novel multifunctional nanoplatform comprising alginate nanogel co-loaded with cisplatin and gold nanoparticles (AuNPs) has been firstly developed to combine photothermal therapy and chemotherapy. The antitumor efficacy of the as-prepared nanocomplex was tested against CT26 colorectal tumor model. The nanocomplex showed an improved chemotherapy efficacy than free cisplatin and caused a significantly higher tumor inhibition rate. The in vivo thermometry results indicated that the tumors treated with the nanocomplex had faster temperature rise rate under 532 nm laser irradiation and received dramatically higher thermal doses due to optical absorption properties of AuNPs. The combined action of chemo-photothermal therapy using the nanocomplex dramatically suppressed tumor growth up to 95% of control and markedly prolonged the animal survival rate. Moreover, tumor metabolism was quantified by [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose)-positron emission tomography (PET) imaging and revealed that the combination of the nanocomplex and laser irradiation have the potential to eradicate microscopic residual tumor to prevent cancer relapse. Therefore, the nanocomplex can afford a potent anticancer efficacy whereby heat and drug can be effectively deliver to the tumor, and at the same time the high dose-associated side effects due to the separate application of chemotherapy and thermal therapy could be potentially reduced.

Gold-coated iron oxide nanoparticles trigger apoptosis in the process of thermo-radiotherapy of U87-MG human glioma cells.

Recently, gold-coated iron oxide nanoparticles (Au@IONPs) have received a great deal of attention in cancer therapy. In this in vitro study we aimed to investigate the anti-cancer effects of Au@IONPs core-shell nanoparticles when applied in thermo-radiotherapy. Moreover, we investigated the level of apoptosis induced in U87-MG human glioma cells after receiving a combinatorial treatment regimen (Au@IONPs + hyperthermia + radiotherapy). Firstly, the Au@IONPs nanocomplex was prepared and characterized. Cytotoxicity of the nanoparticles (various concentrations; 4 h incubation time) was investigated on U87-MG cells and finally the concentrations of 10 and 15 µg/mL were selected for further studies. After incubation of the cells with nanoparticles, they received hyperthermia (43 °C; 1 h) and then were immediately exposed to 6 MV X-ray (2 and 4 Gy). Following the treatments, MTT assay was used to analyze cell viability and flow cytometry was used to determine the level of apoptosis in each treatment group. The results revealed that nanoparticles have no significant cytotoxicity at concentrations lower than 10 µg/mL. Also, we observed that nanoparticles are able to enhance the cytotoxic effect of hyperthermia and radiation. The major mode of cell death was apoptosis when nanoparticles, hyperthermia and radiation were concomitantly applied to cancer cells. In conclusion, Au@IONP nanoparticle can be considered as a good thermo-radio-sensitizer which triggers significant levels of apoptosis in cancer therapy. In this in vitro study, we report the anti-cancer effects of gold-coated iron oxide nanoparticles (Au@IONPs) when applied in thermo-radiotherapy.

Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats.

The major side effect of gentamicin (GEN) is nephrotoxicity which in turn restricts the clinical use of this drug. In this study, the effect of gallic acid (GA) on gentamicin-induced nephrotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups: control, GEN (100 mg/kg/day), GEN + GA (30 mg/kg/day), GA (30 mg/kg/day). All drug administrations were done intraperitoneally (i.p) for eight consecutive days. Twenty-four hours after the last administration, blood samples were collected to determine serum creatinine (Cr), blood urea nitrogen (BUN). The right kidney was used for histological examination. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were assayed in left renal tissue. Results showed a significant increase in the levels of MDA, NO, Cr, and BUN and decrease of GSH, CAT, GPx, and SOD by GEN administration. Co-administration with GA showed reduction in the levels of MDA, NO, Cr, and BUN and increase in GSH, CAT, GPx, and SOD. Also, the nephroprotective effect of GA was confirmed by the histological examination of the kidneys. The results of our study showed that GA exerts a significant nephroprotective effect against GEN-induced nephrotoxicity.

Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer.

Because of their great scientific and technological potentials, iron oxide nanoparticles (IONPs) have been the focus of extensive investigations in biomedicine over the past decade. Additionally, the surface plasmon resonance effect of gold nanoparticles (AuNPs) makes them a good candidate for photothermal therapy applications. The unique properties of both IONPs (magnetic) and AuNPs (surface plasmon resonance) may lead to the development of a multi-modal nanoplatform to be used as a magnetic resonance imaging (MRI) contrast agent and as a nanoheater for photothermal therapy. Herein, core-shell gold-coated IONPs (Au@IONPs) were synthesized and investigated as an MRI contrast agent and as a light-responsive agent for cancer photothermal therapy.The synthesized Au@IONPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. The transverse relaxivity (r 2) of the Au@IONPs was measured using a 3-T clinical MRI scanner. Through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of the Au@IONs was examined on a KB cell line, derived from the epidermal carcinoma of a human mouth. Moreover, the photothermal effects of Au@IONPs in the presence of a laser beam (λ = 808 nm; 6.3 W/cm2; 5 min) were studied.The results show that the Au@IONPs are spherical with a hydrodynamic size of 33 nm. A transverse relaxivity of 95 mM-1 S-1 was measured for the synthesized Au@IONPs. It is evident from the MTT results that no significant cytotoxicity in KB cells occurs with Au@IONPs. Additionally, no significant cell damage induced by the laser is observed. Following the photothermal treatment using Au@IONPs, approximately 70% cell death is achieved. It is found that cell lethality depended strongly on incubation period and the Au@IONP concentration.The data highlight the potential of Au@IONPs as a dual-function MRI contrast agent and photosensitizer for cancer photothermal therapy.

Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of articular cartilage. As chondrocytes are the only cell type forming the articular cartilage, their gradual loss is the main cause of OA. There is a substantial body of published research that suggests reactive oxygen species (ROS) are major causative factors for chondrocyte damage and OA development. Oxidative stress elicited by ROS is capable of oxidizing and subsequently disrupting cartilage homeostasis, promoting catabolism via induction of cell death and damaging numerous components of the joint. IL-1ß and TNF-α are crucial inflammatory factors that play pivotal roles in the pathogenesis of OA. In this process, the mitochondria are the major source of ROS production in cells, suggesting a role of mitochondrial dysfunction in this type of arthritis. This may also be promoted by inflammatory cytokines such as IL-1ß and TNF-α which contribute to chondrocyte death. In patients with OA, the expression of endoplasmic reticulum (ER) stress-associated molecules is positively correlated with cartilage degeneration. Melatonin and its metabolites are broad-spectrum antioxidants and free radical scavengers which regulate a variety of molecular pathways such as inflammation, proliferation, apoptosis, and metastasis in different pathophysiological situations. Herein, we review the effects of melatonin on OA, focusing on its ability to regulate apoptotic processes and ER and mitochondrial activity. We also evaluate likely protective effects of melatonin on OA pathogenesis.

Melatonin synergistically enhances protective effect of atorvastatin against gentamicin-induced nephrotoxicity in rat kidney.

The risk of serious side-effects such as nephrotoxicity is the principal limitation of gentamicin (GEN) therapeutic efficacy. Oxidative stress is considered to be an important mediator of GEN-induced nephrotoxicity. The present study was designed to evaluate the efficacy of the combination of melatonin (MT) plus atorvastatin (ATO) against GEN-induced nephrotoxicity in rats. We utilized 30 male Wistar albino rats allocated in 5 groups, each containing 6 rats: control, GEN (100 mg/kg/day), ATO (10 mg/kg/day) + GEN, MT (20 mg/kg/day) + GEN, and ATO (10 mg/kg/day) plus MT (20 mg/kg/day) + GEN. Kidney weight, serum creatinine and urea concentration, renal ROS, MDA, GSH levels, SOD, and CAT activity were determined. GEN-induced nephrotoxicity was evidenced by marked elevations in serum urea and creatinine, kidney weight, renal ROS, and MDA levels and reduction in renal GSH level, SOD and CAT activity. MT pretreatment significantly lowered the elevated serum creatinine concentration, kidney weight, renal ROS and MDA levels. However ATO could not reduce these parameters, but similarly to MT, it was able to enhance the renal GSH level, CAT and SOD activity. In addition, a combination therapy of MT plus ATO enhanced the beneficial effects of ATO, while not changing the effects of MT effects or even improving them. The present study indicates that a combination therapy of MT plus ATO can attenuate renal injury in rats treated with GEN, possibly by reducing oxidative stress, and it seems that MT can enhance the beneficial effects of ATO.

Physico-chemical and MR relaxometry study of bovine serum albumin-coated magneto-plasmonic nanoparticles designed for potential use in cancer nanotheranostics.

PURPOSE: In recent years, the use of nanoparticles has been developed to improve MRI contrast. To improve the contrast agents in image-guided therapy by Multifunctional nanoparticles, in this study, we synthesized a theranostic magneto-plasmonic nanocomplex based on magnetic iron oxide nanoparticles and bovine serum albumin-modified gold nanorod (Au@BSA-Fe3O4@CMD). The purpose of synthesizing these nanoparticles was to use them as MRI contrast agent and photothermal agents in in vitro and in vivo experiments. MATERIALS AND METHODS: Initially, the properties of the synthesized nanoparticles were investigated by methods such as DLS, TEM, FTIR. MTT assay was used to evaluate the toxicity of nanoparticles. Finally, to evaluate the contrast ability of nanoparticles, MRI images were taken in in vitro and in vivo conditions and then the images were analyzed. RESULTS: MTT test results on CT26 cell line showed no significant cytotoxicity for Au@BSA-Fe3O4@CMD nanoparticles at concentrations up to 20 ppm. The in vitro results demonstrated that the Au@BSA-Fe3O4@CMD nanocomplex has high T2 relaxation rate and great relaxivities (r2 = 140.14 mM-1 s-1, r1 = 2.066 mM-1 s-1, r2/r1 = 67.83). For in vivo conditions, a decrease in T2 signal of 9.64 and 11.01, respectively, was observed for intratumoral and intraperitoneal injection of nanoparticles. CONCLUSION: These in vitro and in vivo studies show that Au @ BSA-Fe3O4@CMD nanoparticles can significantly reduce the signal intensity of T2-weight MRI images, and therefore can offer significant potential as a theranostic platform for effective tumor MR imaging.

The future opportunities and remaining challenges in the application of nanoparticle-mediated hyperthermia combined with chemo-radiotherapy in cancer.

A pivotal cause of death in the modern world, cancer is an insidious pathology that should be diagnosed at an early stage for successful treatment. Development of therapeutic interventions with minimal invasiveness and high efficacy that can discriminate between tumor and normal cells is of particular interest to the clinical science, as they can enhance patient survival. Nanoparticles are an invaluable asset that can be adopted for development of such diagnostic and therapeutic modalities, since they come in very small sizes with modifiable surface, are highly safe and stable, and can be synthesized in a controlled fashion. To date, different nanoparticles have been incorporated into numerous modalities such as tumor-targeted therapy, thermal therapy, chemotherapy, and radiotherapy. This review article seeks to deliver a brief account of recent advances in research and application of nanoparticles in hyperthermia-based cancer therapies. The most recent investigations are summarized to highlight the latest advances in the development of combined thermo-chemo-radiotherapy, along with the challenges associated with the application of nanoparticles in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Folate functionalized gold-coated magnetic nanoparticles effect in combined electroporation and radiation treatment of HPV-positive oropharyngeal cancer.

The rate of HPV-positive oropharyngeal cancer incidence is increasing, especially in the young population. While these patients show good responses to radiotherapy. The major complication of radiotherapy is normal tissue involvement. Thus, finding an effective treatment method is essential. Multimodal therapy with the lowest side effect could be an effective treatment method. Theranostic gold magnetic core-shell nanostructure was developed as a platform for multimodal therapy of HPV-positive oropharyngeal cancer. The folate functionalized gold-magnetic core-shell nanostructure has been synthesized in a stepwise approach and characterized with various techniques including TEM, UV-Vis, and FTIR spectroscopy. KB was selected as a host for HPV and folate receptor-positive cancer. HGF as normal cell lines was selected. Both cell lines have been treated with nanoparticles, electric field and radiotherapy, either separately or in combination. Cell viability and apoptosis rate were determined by MTT and flow cytometry assay. In addition, cellular uptake of the nanoparticles was measured by ICP-OES analysis. The average size of folate functionalized gold-magnetic core-shell nanostructure was 13.8 ± 6.4 nm. A characteristic plasmonic peak of gold nanoshells was observed in the UV-Vis spectrum. The functionalization of synthesized nanostructure was confirmed with FTIR spectroscopy. None of the treatments alone can cause a significant death in cancerous cells. Combination treatments can increase cancer cell mortality and increase the proportion of apoptotic cells in them. Furthermore, it has been observed that the electric field enhanced the cellular uptake of nanoparticles just in cancerous cells. Based on our findings, we conclude that the combination of folate functionalized nanoparticles and electroporation opens a new way to improve radiation therapy efficacy of HPV-positive cancers.