Anti-VCAM-1 and Anti-IL4Rα Aptamer-Conjugated Super Paramagnetic Iron Oxide Nanoparticles for Enhanced Breast Cancer Diagnosis and Therapy.

The surface protein overexpressed on cancer cells can be used as biomarkers for early detection of specific diseases. Anti-VCAM-1 and anti-IL4Rα DNA aptamers specific to VCAM-1 and IL4Rα receptors that are overexpressed in 4T1 tumor-bearing mice could be used as potential biomarker for both diagnostic and therapeutic applications in cancer biology. Cell Viability and luciferase assay of 4T1-Luc2 cancer cells in the presence of anti-VCAM-1 ssDNA or anti-IL4Rα RNA aptamers was assessed by monitoring the changes in the absorbance and the fluorescence of Alamar blue dye. The aptamer-conjugated SPIO magnetic beads, used for the selective targeting to tumor sites, were monitored using noninvasive MRI and Bioluminescence imaging (BLI). Cell viability and luciferase assays showed that both anti-VCAM-1 and anti-IL4Rα aptamers favor the depletion of cancer cells and limit tumor progression. Microscopic analyses confirmed that the target specific aptamers significantly trigger tumor cell apoptosis and limit cancer cell growth in vitro. The intravenous injection of SPIO nanoparticle-conjugated aptamers were further confirmed using noninvasive MRI and Bioluminescence imaging. Anti-VCAM1 and anti-IL4Rα aptamers, specific to VCAM-1 and IL4Rα receptors overexpressed in 4T1-Luc2 tumor-bearing mice, were used as diagnostic and therapeutic tools.

siRNA Conjugated Nanoparticles-A Next Generation Strategy to Treat Lung Cancer.

Despite major progress in both therapeutic and diagnostic techniques, lung cancer is still considered the leading cause of cancer mortality in the world due to the ineffectiveness of the classical treatments used nowadays. Luckily, the discovery of small interfering RNA (siRNA) planted hope in the hearts of scientists and patients worldwide as a new breakthrough in the world of oncology and a robust tool for finally curing cancer. However, the valuable siRNA must be protected and preserved to ensure the effectiveness of this gene therapy, thus nanoparticles are gaining more attention than previous years as the optimal carriers for this fragile molecule. siRNA-loaded nanoparticles are being extensively investigated to find the appropriate formulation, combination, and delivery route with one objective in mind-successfully overcoming all possible limitations shown in clinical studies and making full use of this novel technique to become the next generation treatment to wipe out many chronic diseases, including cancer. In this review, the benefits of using siRNA and nanoparticles in lung cancer treatment will be globally reviewed before discussing why and how nanoparticles and siRNA can be combined to achieve an efficient treatment of lung cancer for prospective clinical applications.

Effect of polyethylene glycol surface charge functionalization of SWCNT on the in vitro and in vivo nanotoxicity and biodistribution monitored noninvasively using MRI.

The current study evaluated in vitro and in vivo toxicity of carboxyl or amine polyethylene glycol (PEG) surface functionalization of single-walled carbon nanotubes (SWCNTs). Assessments of cytotoxicity, genotoxicity, immunotoxicity, and oxidative stress were performed in vitro and in vivo (in a 1-month follow-up study). The SWCNT biodistribution was investigated using noninvasive magnetic resonance imaging (MRI). Results confirmed the enhanced biocompatibility of PEG-functionalized SWCNTs compared to non-functionalized materials with significant decreases (p < 0.05) in the percentage of cell viability and increases in ROS generation, mitochondrial membrane potential, cell apoptosis, oxidative stress generation, and oxidative DNA damage in vitro. PEG-functionalized SWCNTs with amine terminals were found to induce prominent increases in ROS generation, mitochondrial membrane potential, and oxidative stress compared to carboxy functionalization. No significant difference in the biodistribution of either functionalized SWCNTs was observed in MRI. In vivo assessments revealed a statistically significant increase (p < 0.05) in oxidative stress as early as 24 h in serum and liver; however, all values normalized at 2 weeks' investigation time point. DNA damage was minimal with either PEG-COOH or PEG-NH2 functionalized SWCNTs after 2 weeks' exposure. The negatively charged SWCNTs caused lesser DNA damage compared to positively charged samples. Carboxy-functionalized SWCNTs did not cause substantial changes in inflammatory mediators and were found to be significantly safer than non-functionalized SWCNTs and may pave the way for novel biomedical applications in cancer diagnosis and therapy.

Intrapulmonary administration of bone-marrow derived M1/M2 macrophages to enhance the resolution of LPS-induced lung inflammation: noninvasive monitoring using free-breathing MR and CT imaging protocols.

BACKGROUND: Alveolar macrophages, with their high functional plasticity, were reported to orchestrate the induction and resolution of inflammatory processes in chronic pulmonary diseases. Noninvasive imaging modalities that offer simultaneous monitoring of inflammation progression and tracking of macrophages subpopulations involved in the inflammatory cascade, can provide an ideal and specific diagnostic tool to visualize the action mechanism in its initial stages. Therefore, the purpose of the current study was to evaluate the role of M1 and M2 macrophages in the resolution of lipopolysaccharide (LPS)-induced lung inflammation and monitor this process using noninvasive free-breathing MRI and CT protocols. METHODS: Bone-marrow derived macrophages were first polarized to M1 and M2 macrophages and then labeled with superparamagnetic iron oxide nanoparticles. BALB/c mice with lung inflammation received an intrapulmonary instillation of these ex vivo polarized M1 or M2 macrophages. The biodistribution of macrophages subpopulations and the subsequent resolution of lung inflammation were noninvasively monitored using MRI and micro-CT. Confirmatory immunohistochemistry analyses were performed on lung tissue sections using specific macrophage markers. RESULTS: As expected, large inflammatory areas noninvasively imaged using pulmonary MR and micro-CT were observed within the lungs following LPS challenge. Subsequent intrapulmonary administration of M1 and M2 macrophages resulted in a significant decrease in inflammation starting from 72 h. Confirmatory immunohistochemistry analyses established a progression of lung inflammation with LPS and its subsequent reduction with both macrophages subsets. An enhanced resolution of inflammation was observed with M2 macrophages compared to M1. CONCLUSIONS: The current study demonstrated that ex vivo polarized macrophages decreased LPS-induced lung inflammation. Noninvasive free-breathing MR and CT imaging protocols enabled efficient monitoring of progression and resolution of lung inflammation.

Knowledge, attitude, and readiness of pharmacists toward medication therapy management for patients with attention deficit hyperactivity disorder: a cross-sectional quantitative study.

BACKGROUND: Medication Therapy Management (MTM) is a patient-centered service that optimizes drug therapy, improves clinical outcomes, and enhances quality of life. Pharmacists play a critical role in MTM services and provide comprehensive medication management for patients with attention deficit hyperactivity disorder (ADHD). AIM: The aim of this study was to assess the knowledge, attitude, and readiness of Iraqi community pharmacists regarding MTM services for ADHD patients. METHOD: A cross-sectional study was conducted among 480 Iraqi pharmacists working in community pharmacies in Baghdad. Data were collected using a pre-validated, self-administered questionnaire with 34 items. RESULTS: Results showed that only 127 (26.5%) pharmacists had good knowledge, 146 (30.4%) had good attitude, and 148 (30.8%) had high readiness regarding MTM services in ADHD patients. Multivariate analyses showed that a higher number of hours worked per week in the hospital was significantly associated with a lower likelihood of high attitude, whereas practicing MTM services, high knowledge, and high attitude were significantly associated with a higher likelihood of high readiness. CONCLUSION: The findings of this study indicate that knowledge, attitudes, and readiness for MTM services for ADHD patients are inadequate. Therefore, there is an urgent need for effective educational strategies to better prepare pharmacists for their potential role in the community, particularly for providing MTM services to ADHD patients.

Assessing the accuracy and consistency of ChatGPT in clinical pharmacy management: A preliminary analysis with clinical pharmacy experts worldwide.

BACKGROUND: ChatGPT conversation system has ushered in a revolutionary new era of information retrieval and stands as one of the fastest-growing platforms. Clinical pharmacy, as a dynamic discipline, necessitates an advanced comprehension of drugs and diseases. The process of decision-making in clinical pharmacy demands accuracy and consistency in medical information, as it directly affects patient safety. OBJECTIVE: The objective was to evaluate ChatGPT's accuracy and consistency in managing pharmacotherapy cases across multiple time points. Additionally, input was gathered from global clinical pharmacy experts, and the agreement between ChatGPT's responses and those of clinical pharmacy experts worldwide was assessed. METHODS: A set of 20 cases of pharmacotherapy was entered into ChatGPT at three different time points. Reliability analysis was performed using inter-rater reliability to measure the accuracy of the output generated by ChatGPT at each time point. Test-retest reliability was performed to measure the consistency of the output generated by ChatGPT across the three time points. Pharmacy expert performance was evaluated, and the overall results were compared. RESULTS: ChatGPT achieved a hit rate of 70.83% at week 1, 79.2% at week 3, and 75% at week 5. The percent agreement between weeks 1 and 3 was 79.2%, whereas it was 87.5% between weeks 3 and 5, and 83.3% between weeks 1 and 5. In contrast, accuracy rates among clinical pharmacy experts showed considerable variation according to their geographic location. The highest agreement between clinical pharmacist responses and ChatGPT responses was observed at the last time point examined. CONCLUSIONS: Overall, the analysis suggested that ChatGPT is capable of generating clinically relevant pharmaceutical information, albeit with some variation in accuracy and consistency. It should be noted that clinical pharmacy experts worldwide may provide varying degrees of accuracy depending on their expertise. This study highlights the potential of AI chatbots in clinical pharmacy.

Endothelial cell-derived microparticles loaded with iron oxide nanoparticles: feasibility of MR imaging monitoring in mice.

PURPOSE: To assess the feasibility of loading iron oxide nanoparticles in endothelial microparticles (EMPs), thereby enabling their noninvasive monitoring with magnetic resonance (MR) imaging in mice. MATERIALS AND METHODS: Experiments were approved by the French Ministry of Agriculture. Endothelial cells, first labeled with anionic superparamagnetic nanoparticles, were stimulated to generate EMPs, carrying the nanoparticles in their inner compartment. C57BL/6 mice received an intravenous injection of nanoparticle-loaded EMPs, free nanoparticles, or the supernatant of nanoparticle-loaded EMPs. A 1-week follow-up was performed with a 4.7-T MR imaging device by using a gradient-echo sequence for imaging spleen, liver, and kidney and a radial very-short-echo time sequence for lung imaging. Comparisons were performed by using the Student t test. RESULTS: The signal intensity loss induced by nanoparticle-loaded EMPs or free nanoparticles was readily detected within 5 minutes after injection in the liver and spleen, with a more pronounced effect in the spleen for the magnetic EMPs. The kinetics of signal intensity attenuation differed for nanoparticle-loaded EMPs and free nanoparticles. No signal intensity changes were observed in mice injected with the supernatant of nanoparticle-loaded EMPs, confirming that cells had not released free nanoparticles, but only in association with EMPs. The results were confirmed by using Perls staining and immunofluorescence analysis. CONCLUSION: The strategy to generate EMPs with magnetic properties allowed noninvasive MR imaging assessment and follow-up of EMPs and opens perspectives for imaging the implications of these cellular vectors in diseases.

Cross-sectional study of the knowledge, perception and attitude of first-year university students in Iraq towards SARS-CoV-2 Omicron variant and COVID-19 vaccines.

OBJECTIVES: The aim of this study was to first assess the knowledge and perception of first-year university students in Iraq about COVID-19 in general and SARS-CoV-2 latest variant of concern, and to evaluate the attitudes towards protection measures including vaccination. STUDY DESIGN: A cross-sectional study was conducted among newly enrolled students at the American University of Iraq-Baghdad. Mann-Whitney U and Kruskal-Wallis tests were used to test an association between the outcomes measured on a 5-point Likert scale and the binary and the categorical independent variables, respectively. χ2 test was used to test the association between nominal categorical variables, while Kendall's τ-b was used for ordinal variables. PARTICIPANTS: Students (n=432) were invited to fill out a survey specifically tailored to assess their knowledge, perception and attitude towards Omicron variant and COVID-19 vaccines acceptance. 363 students enrolled in various majors participated in this study. RESULTS: Assessment of COVID-19 knowledge and perception revealed that students still lack reliable info and data about FDA-approved treatment options (70.5%), SARS-CoV-2 variants (96.5%) and approved vaccines. Students' attitude and practices towards recommended safety measures should be reassessed to better manage the pandemic. Adherence level was shown to be associated with the belief in its capacity to effectively manage the new variant. Interestingly, 85% of the students have received at least one dose of approved vaccine. A significant positive correlation was detected between the level of adherence to recommended precautions and the intention to take a third booster shot if proven effective. CONCLUSIONS: Students' reliable knowledge about COVID-19 pandemic including the various strains and approved vaccines should be improved to better manage the pandemic and set foundations for a more appropriate approach when another pandemic occurs. Special workshops should be organised to ensure that students and the public have a more trusted source of information about COVID-19.

Detection of Radiolabeled Inflammatory Cell Macrophage Subpopulations in Chronic Respiratory Diseases: Results from Preliminary Analyses.

Chronic respiratory diseases (CRDs) like asthma and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality worldwide. Alveolar macrophages (AM) are immune cells that exist in different polarization states/phenotypes and have been shown to play a critical role during an inflammatory process. In this paper, differently polarized mouse bone marrow-derived macrophages (BMDM (M1-proinflammatory or M2-immunomodulator)) were radiolabeled with either 99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO), 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG), or 67Ga-citrate. Biocompatibility and in vivo biodistribution of radionuclide-labeled macrophages after intravenous injection were evaluated. Radioactivity measurements were performed using Packard Cobra Quantum 5002 Gamma Counter. Both M1 and M2 macrophages showed a higher uptake for 18F-FDG and 99mTc-HMPAO, than 67Ga-citrate. M2 macrophages showed a higher uptake of radionuclides than M1 macrophages. The used radionuclides were biocompatible for both M1 and M2 macrophages. At 2-hour postinjection, 18F-FDG-labeled M1 and M2 macrophages were found significantly higher in the lung of inflammatory animals (12.54 ± 1.58% and 14.13 ± 1.03%, respectively) than in control mice. Labeling macrophages with either 18F-FDG or 99mTc-HMPAO did not affect their biodistribution. The results from these initial experiments indicate that radionuclide-labeled macrophages may allow a higher sensitivity detection in nuclear imaging techniques such as PET and SPECT. Further confirmatory studies are needed to noninvasively image radiolabeled BMDM to understand their role in the inflammatory processes inherent to CRDs.

Positive contrast with therapeutic iron nanoparticles at 4.7 T.

OBJECT: The purpose of the study was to show the feasibility of a positive contrast technique GRadient echo Acquisition for Superparamagnetic particles with Positive contrast (GRASP), for a specific type of magnetic particles, designed for tumor treatment under MRI monitoring. MATERIALS AND METHODS: A simulation study was performed to estimate field inhomogeneity intensities induced by increasing concentrations of particles at different static fields. The GRASP sequence was setup on a 4.7 T Bruker system during an in vitro study. Six mice, included in the in vivo study received particles in the left calf muscle and contrast enhancement values, were measured over three time points, for both negative and positive contrast images. RESULTS: Comparing values obtained by simulation at 1.5, 3, and 4.7 T, the strongest susceptibility effect was obtained at 4.7 T. Based on simulation and in vitro data, gradient settings were chosen for in vivo imaging. GRASP resulted in bright regions at and around the injection site, and higher enhancement values, compared to standard GRE imaging. Both contrasts were useful for longitudinal follow-up, with a faster decay over time for GRASP. CONCLUSION: The magnetic nanoparticles for drug delivery can be detected using positive contrast. Combining imaging sequences, i.e., negative contrast and susceptibility methods, increased imaging specificity of large magnetic particles and enabled their follow-up for theranostic applications.

Shedding Light on the Direct and Indirect Impact of the COVID-19 Pandemic on the Lebanese Radiographers or Radiologic Technologists: A Crisis within Crises.

With the novel coronavirus disease 2019 (COVID-19) pandemic, the need for radiologic procedures is increasing for the effective diagnosis and follow-up of pulmonary diseases. There is an immense load on the radiographers' shoulders to cope with all the challenges associated with the pandemic. However, amidst this crisis, Lebanese radiographers are also suffering from a socioeconomic crisis and record hyperinflation that have posed additional challenges. A cross-sectional study was conducted among registered Lebanese radiographers to assess the general, workplace conditions, health and safety, mental/psychologic, financial, and skill/knowledge development impacts. Despite applying an adapted safety protocol, institutions are neither providing free RT-PCR testing to their staff nor showing adequate support for infected staff members, thus causing distress about contracting the virus from the workplace. Aggravated by the deteriorating economic situation that affected the radiographers financially, they additionally suffer from severe occupational physical and mental burnout. Regardless of that, they used their free time during the lockdown for skill/knowledge development and have performed many recreational activities. This cross-sectional study highlighted the different ways the pandemic has impacted the radiographers: physically, psychologically, and financially. It aimed to shed light on what these frontline heroes are passing through in the midst of all these unprecedented crises.

Correlation of Kidney Size on Computed Tomography with GFR, Creatinine and HbA1C for an Accurate Diagnosis of Patients with Diabetes and/or Chronic Kidney Disease.

Diabetes is considered one of the major causes of chronic kidney disease (CKD), affecting renal blood vessels and nerves. Diagnosis of CKD by traditional biochemical serum and blood analyses is insufficient and insensitive, thus requiring the development of a more robust technique. This novel study aims to propose a new method for the accurate diagnosis of CKD, quantification of kidney damage, and its prognosis by physicians by measuring the kidney volume on computed tomography (CT). In total, 251 patients were enrolled in this retrospective study. They were divided into four groups: control, patients having diabetes, patients having CKD, and patients having both diabetes and CKD. Results showed that kidney volume correlated negatively with both GFR and HbA1C on CT images, in addition to decreasing faster in males than females. Moreover, HbA1C was shown to correlate positively with creatinine and negatively with GFR. Finally, GFR was more robust than creatinine when correlated with age. The association between kidney volume with GFR and HbA1c can be used to accurately anticipate kidney volume in established CKD on CT scan, especially in resource-poor settings. Furthermore, HbA1C can serve as a powerful biomarker for studying renal function in diabetic CKD patients as it correlates with creatinine and GFR.

The History, Efficacy, and Safety of Potential Therapeutics: A Narrative Overview of the Complex Life of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed a serious public health concern and started a race against time for researchers to discover an effective and safe therapy for coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2. This review aims to describe the history, efficacy, and safety of five potential therapeutics for COVID-19, remdesivir, favipiravir, hydroxychloroquine, tocilizumab, and convalescent plasma. A literature review was conducted through October 2020 to identify published studies evaluating the efficacy and safety of these five potential therapeutics. Clinical improvement was used to assess the efficacy, while reported withdrawals from study participation and adverse events were used to evaluate the safety. In total, 95 clinical studies (6 interventional and 89 observational studies) were obtained, of which 42 were included in this review. The evaluation of the efficacy and safety profiles is challenging due to the limitations of the clinical studies on one hand, and the limited number of randomized controlled trials (RCTs) on the other. Moreover, there was insufficient evidence to support repurposing remdesivir, favipiravir, and tocilizumab for COVID-19.

Long-term follow-up of lung biodistribution and effect of instilled SWCNTs using multiscale imaging techniques.

Due to their distinctive properties, single-walled carbon nanotubes (SWCNTs) are being more and more extensively used in nanotechnology, with prospects in nanomedicine. It would therefore appear essential to develop and apply appropriate imaging tools for detecting and evaluating their biological impacts with the prospect of medical applications or in the situation of accidental occupational exposure. It has been shown recently that raw SWCNTs with metallic impurities can be noninvasively detected in the lungs by hyperpolarized (3)helium (HP-(3)He) MRI. Moreover raw and purified SWCNTs had no acute biological effect. The purpose of the present longitudinal study was to investigate long-term follow-up by imaging, as well as chronic lung effects. In a 3-month follow-up study, multiscale imaging techniques combining noninvasive HP-(3)He and proton (H) MRI to ex vivo light (histopathological analysis) and transmission electron microscopy (TEM) were used to assess the biodistribution and biological effects of intrapulmonary instilled raw SWCNTs. Specific in vivo detection of carbon nanotubes with MRI relied on their intrinsic metal impurities. MRI also has the ability to evaluate tissue inflammation by the follow-up of local changes in signal intensity. MRI and ex vivo microscopy techniques showed that granulomatous and inflammatory reactions were produced in a time and dose dependent manner by instilled raw SWCNTs.

Optimizing use of theranostic nanoparticles as a life-saving strategy for treating COVID-19 patients.

On the 30th of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats.

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.

Elaboration of PLLA-based superparamagnetic nanoparticles: characterization, magnetic behaviour study and in vitro relaxivity evaluation.

Oleic acid-coated magnetite has been encapsulated in biocompatible magnetic nanoparticles (MNP) by a simple emulsion evaporation method. The different parameters influencing the particles size were studied. Between these parameters, the stirring speed and the polymer concentration were found to influence positively or negatively, respectively, the MNP size which varied between 320 and 1500nm. The magnetite encapsulation efficacy was about than 90% yielding a high magnetite loading of up to 30% (w/w). X-ray diffraction showed that magnetite crystalline pattern was not modified after emulsification and solvent evaporation. The X-ray photoelectron spectroscopy (XPS) results indicated the presence of less than 0.1% of iron atoms at the nanoparticles surface. Vibration simple magnetometer (VSM) showed a superparamagnetic behaviour of the MNP and a saturation magnetization increasing with the increased magnetite amount used in formulation. Moreover, T(1) and T(2) relaxivities of MNP (4.7T, 20 degrees C) were 1.7+/-0.1 and 228.3+/-13.1s(-1)mM(-1), respectively, rendering them in the same category of known negative contrast agents which shorten the T(2) relaxation time. Therefore, by using an appropriate anticancer drug in their formulation, these magnetic nanoparticles can present a promising mean for simultaneous tumor imaging, drug delivery and real time monitoring of therapeutic effect.

SWCNTs as novel theranostic nanocarriers for cancer diagnosis and therapy: towards safe translation to the clinics.

With their unique physicochemical properties, single walled carbon nanotubes (SWCNTs) hold great promise for applications as drug delivery systems (DDS) for early and better diagnosis and therapy of cancer. While several in vitro and in vivo studies have validated their potential benefit, no SWCNT-based formulation has yet reached clinical trials. Towards prospective safe clinical applications, the main properties that were adopted to enhance the biocompatibility of SWCNTs were highlighted. Then, the recent progresses in the in vivo applications of SWCNTs as diagnostic nanoprobes using multimodality imaging techniques and as therapeutic nanocarriers delivering wide range of anticancer efficient drugs to tumors were reviewed. Finally, the efforts required for safe clinical applications of SWCNTs as DDS for cancer diagnosis and therapy were discussed.

Combination of drug-conjugated SWCNT nanocarriers for efficient therapy of cancer stem cells in a breast cancer animal model.

Targeting breast cancer and more specifically cancer stem cell (CSC) subpopulation, responsible for tumor growth, resistance and self-renewal, using combination of therapeutic drugs selectively delivered via biocompatible nanocarriers, provides a novel approach for effective therapy. Here, we propose to evaluate the potential therapeutic efficacy of combining Paclitaxel and Salinomycin drugs actively targeted to both breast cancer and CSCs in xenograft murine model after conjugation with biocompatible CD44 antibody conjugated SWCNTs via hydrazone linker allowing pH-responsive release mechanism near the acidic tumor microenvironment. Both in vitro investigations on MDA-MB-231, sorted CSC negative or CSC positive fractions and in vivo evaluations on tumor-bearing mice using noninvasive bioluminescence and magnetic resonance imaging confirmed the enhanced therapeutic effect of the combined therapy compared to treatment with individual drug-conjugated nanocarriers or free drug suspensions. Thus, confirmed the great promise of the developed SWCNTs drug delivery system for effective breast cancer treatment by targeting and eradicating both whole tumor cells and CSCs populations.

Magnetic Targeting and Delivery of Drug-Loaded SWCNTs Theranostic Nanoprobes to Lung Metastasis in Breast Cancer Animal Model: Noninvasive Monitoring Using Magnetic Resonance Imaging.

PURPOSE: In this study, we aimed to develop novel therapeutic and diagnostic approaches by improving the targeting of doxorubicin-loaded single-walled carbon nanotubes (SWCNTs) to metastatic regions, and monitor their preferential homing and enhanced therapeutic effect using noninvasive free-breathing magnetic resonance imaging (MRI) and bioluminescence imaging. PROCEDURES: High-energy flexible magnets were specifically positioned over the metastatic tumor sites in the lungs. SWCNTs biodistribution, tumor progression, and subsequent treatment efficiency were assessed following administration of the magnetically attracted doxorubicin-loaded anti-CD105 conjugated nanocarriers. RESULTS: The use of high-energy magnets offered improved theranostic effect of doxorubicin-loaded nanocarriers, by magnetically targeting them towards metastatic tumor sites in the lungs. MRI allowed sensitive monitoring of nanocarriers biodistribution in the abdominal organs, their preferential homing towards the metastatic sites, and their enhanced therapeutic effect. CONCLUSIONS: Combination of noninvasive MRI to localize sensitively the tumor sites, with specific positioning of magnets that can enhance the magnetic targeting of nanocarriers, allowed increasing the treatment efficiency.