HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.

Inhibiting HER3 Hyperphosphorylation in HER2-Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells.

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.

Novel Gold Nanorods@Thiolated Pectin on the Killing of HeLa Cells by Photothermal Ablation.

Gold nanorods (AuNRs) have attracted attention in the field of biomedicine, particularly for their potential as photothermal agents capable of killing tumor cells by photothermic ablation. In this study, the synthesis of novel AuNRs stabilized with thiolated pectin (AuNR@SH-PEC) is reported. To achieve this, thiolated pectin (SH-PEC) was obtained by chemically binding cysteamine motifs to the pectin backbone. The success of the reaction was ascertained using FTIR-ATR. Subsequently, the SH-PEC was used to coat and stabilize the surface of AuNRs (AuNR@SH-PEC). In this context, different concentrations of SH-PEC (0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mg/mL) were added to 0.50 mL of AuNRs suspended in CTAB, aiming to determine the experimental conditions under which AuNR@SH-PEC maintains stability. The results show that SH-PEC effectively replaced the CTAB adsorbed on the surface of AuNRs, enhancing the stability of AuNRs without affecting their optical properties. Additionally, scanning electron and atomic force microscopy confirmed that SH-PEC is adsorbed into the surface of the AuNRs. Importantly, the dimension size (60 × 15 nm) and the aspect ratio (4:1) remained consistent with those of AuNRs stabilized with CTAB. Then, the photothermal properties of gold nanorods were evaluated by irradiating the aqueous suspension of AuNR@SH-PEC with a CW laser (808 nm, 1 W). These results showed that photothermal conversion efficiency is similar to the photothermal conversion observed for AuNR-CTAB. Lastly, the cell viability assays confirmed that the SH-PEC coating enhanced the biocompatibility of AuNR@SH-PEC. Most important, the viability cell assays subjected to laser irradiation in the presence of AuNR@SH-PEC showed a decrease in the cell viability relative to the non-irradiated cells. These results suggest that AuNRs stabilized with thiolated pectin can potentially be exploited in the implementation of photothermal therapy.

Pluronic F127 and P104 Polymeric Micelles as Efficient Nanocarriers for Loading and Release of Single and Dual Antineoplastic Drugs.

The potential application of biodegradable and biocompatible polymeric micelles formed by Pluronic F127 and P104 as nanocarriers of the antineoplastic drugs docetaxel (DOCE) and doxorubicin (DOXO) is presented in this work. The release profile was carried out under sink conditions at 37 °C and analyzed using the Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin diffusion models. The cell viability of HeLa cells was evaluated using the proliferation cell counting kit CCK-8 assay. The formed polymeric micelles solubilized significant amounts of DOCE and DOXO, and released them in a sustained manner for 48 h, with a release profile composed of an initial rapid release within the first 12 h followed by a much slower phase the end of the experiments. In addition, the release was faster under acidic conditions. The model that best fit the experimental data was the Korsmeyer-Peppas one and denoted a drug release dominated by Fickian diffusion. When HeLa cells were exposed for 48 h to DOXO and DOCE drugs loaded inside P104 and F127 micelles, they showed lower IC50 values than those reported by other researchers using polymeric nanoparticles, dendrimers or liposomes as alternative carriers, indicating that a lower drug concentration is needed to decrease cell viability by 50%.

Evaluation of a polymeric topical formulation of Endoxifen in an estrogen receptor positive breast cancer murine model.

Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.

[The Mexican Board of Pathology: microscopy examination before and after digital microscopy]. / Consejo Mexicano de Médicos Anatomopatólogos: su examen de microscopia, antes y después de su digitalización.

INTRODUCTION: The examination carried out by the COMMAP for the certification process assessed pathologist formed in dissimilar institutions. In 2007 COMMAP's governing body in turn, decided to digitize it. The purpose of this study is to investigate whether the conversion to virtual slides in the microscopy section, compared with the traditional have had an impact on the scores of the candidates. METHOD: The slides were scanned with high resolution. The virtual microscope is a standard computer screen where there is a program (Aperio Scope Image Viewer) that can display the scanned slides. The results of the microscopy section of the past nine years were compared; two groups were formed: 1) those without digitized examination, and 2) with it. The results were compared by Student t-test and Mann-Whitney. RESULTS: Of a 461 results 240 belonged to the first group and 221 to the second one. On a scale of 1-10, the average scores were 6.6 and 6.8, respectively (p > 0.6 and > 0.5).The minimum and maximum scores were also similar in each group. CONCLUSIONS: According to the results, the digitized exam in the COMMAP's certification process shows no difference between the digitized and the conventional versions.

High antibacterial performance of hydrophobic chitosan-based nanoparticles loaded with Carvacrol.

Bacterial infections have become one of the top ten public health concerns worldwide. These problems are aggravated with the emergence of multi-drug resistant bacterial strains. Thus, it is necessary to adopt novel technological strategies, such as development of bionanomaterials to prevent the infection, and treat this kind of bacteria. At this regard, the chemical modification of chitosan (Cs), by the covalent attachment of a hydrocarbon chain (octanoic acid), was developed to obtain hydrophobic chitosan (HCs). Then, HCs was used to synthetize nanoparticles using the well-known ionotropic gelation approach, optimizing the parameters, such as the TPP/HCs ratio and pH solution to get stable nanoparticles. Then, carvacrol (CAR) was loaded into NPs (HCs-CAR NPs) using different concentrations of 25%, 50% and 75% (%w/w CAR/HCs). The physicochemical properties for HCs-CAR NPs prepared at 50% of CAR stood out from the rest, showing a spherical morphology, with a size of 200 nm, Z potential of 10.4 mV and encapsulation efficiency of 56.28%. These formulations were chosen to evaluate the antibacterial activity, using Gram-negative (Escherichia coli) and Gram-positive bacterial model (Staphylococcus aureus). The HCs-CAR NPs showed great activity against both bacterial models, being more effective against Gram (+) strain (S. aureus), suggesting the potential application of these NPs as novel biomaterial to treat bacterial infection.

One-dimensional magnetic nanowires obtained by protein fibril biotemplating.

Magnetic nanowires were obtained through the in situ synthesis of magnetic material by Fe-controlled nanoprecipitation in the presence of two different protein (human serum albumin (HSA) and lysozyme (Lys)) fibrils as biotemplating agents. The structural characteristics of the biotemplates were transferred to the hybrid magnetic wires. They exhibited excellent magnetic properties as a consequence of the 1D assembly and fusion of magnetite nanoparticles as ascertained by SQUID magnetometry. Prompted by these findings, we also checked their potential applicability as MRI contrast agents. The magnetic wires exhibited large r(2)* relaxivities and sufficient contrast resolution even in the presence of an extremely small amount of Fe in the magnetic hybrids, which would potentially enable their use as T(2) contrast imaging agents.

Microfluidics-assisted conjugation of chitosan-coated polymeric nanoparticles with antibodies: Significance in drug release, uptake, and cytotoxicity in breast cancer cells.

Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a polydimethylsiloxane (PDMS) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2), to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2 + breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties.

Study of the interaction of folic acid-modified gold nanorods and fibrinogen through microfluidics: implications for protein adsorption, incorporation and viability of cancer cells.

Gold nanoparticles (GNPs) are an attractive nanomaterial for potential applications in therapy and diagnostics due to their capability to direct toward specific sites in the organism. However, when exposed to plasma, GNPs can interact with different biomolecules that form a dynamic nano-bio interface called a "protein corona" (PC). Remarkably, the PC could affect multiple biological processes, such as cell targeting and uptake, cytotoxicity, and nanoparticle (NP) clearance. The interaction of nanomaterials with plasmatic proteins has been widely studied under bulk conditions, however, under dynamic conditions, it has just recently been explored. Thus, to mimic a dynamic natural environment found in arteries and veins, microfluidic devices were used. In this work, gold nanorods (GNRs) were synthesized and conjugated with polyethylene glycol (PEG) to reduce their interaction with plasma proteins and increase their biocompatibility. Then, GNRs were functionalized with folic acid, a targeting ligand typically used to recognize tumor cells. The resulting nanosystem was exposed to fibrinogen (FB) to study the development and biological impact of PC formation through two strategies: bulk and laminar flow conditions. The obtained nanosystems were characterized by absorption spectrophotometry, DLS, laser Doppler microelectrophoresis, neutron activation analysis, circular dichroism spectroscopy and TEM. Finally, cell viability and cellular uptake assays were performed to study the influence of the PC on the cell viability and delivery of nanosystems.

Selective estrogen receptor modulators in the prevention of breast cancer in premenopausal women: a review.

The detection of premenopausal women at high risk of breast cancer is key to chemoprevention. Therapy with selective estrogen receptor modulators (SERMs) induces a significant antiproliferative effect in estrogen receptor (ER) positive breast cancer. This review was designed according the guidelines of the 2009 PRISMA statement. Searching different databases, including PubMed, MedlinePlus, PLoS One, Cochrane Breast Cancer Specialized Register, Clinical Trials.gov and American Society of Clinical Oncology. From 168 records screened, 15 full text articles were assessed for eligibility and only 7 studies met the inclusion criteria. Three of the studies included analyzed changes in Ki-67 expression, revealing weaker expression after treatment with acolbifene and raloxifene (P<0.001). Three studies also analyzed the breast volume by magnetic resonance imagining (MRI) and demonstrate a significant difference after 1 year with raloxifene treatment (P=0.0017). Moreover, a 20% reduction in breast density was observed after a 2-year treatment with tamoxifen in premenopausal women. SERMs reduce the risk of developing breast cancer. The studies reviewed here demonstrate the modulation of Ki-67 expression and changes in breast density, suggesting an important preventive role for this group of drugs in prevention for premenopausal women at high risk of developing breast cancer.

Biodegradable photoresponsive nanoparticles for chemo-, photothermal- and photodynamic therapy of ovarian cancer.

Ovarian cancer (OC) is the deadliest gynecological cancer. Standard treatment of OC is based on cytoreductive surgery followed by chemotherapy with platinum drugs and taxanes; however, innate and acquired drug-resistance is frequently observed followed by a relapse after treatment, thus, more efficient therapeutic approaches are required. Combination therapies involving phototherapies and chemotherapy (the so-called chemophototherapy) may have enhanced efficacy against cancer, by attacking cancer cells through different mechanisms, including DNA-damage and thermally driven cell membrane and cytoskeleton damage. We have designed and synthesized poly(lactic-co-glycolic) nanoparticles (PLGA NPs) containing the chemo-drug carboplatin (CP), and the near infrared (NIR) photosensitizer indocyanine green (ICG). We have evaluated the drug release profile, the photodynamic ROS generation and photothermal capacities of the NPs. Also, the antitumoral efficiency of the NPs was evaluated using the SKOV-3 cell line as an in vitro OC model, observing an enhanced cytotoxic effect when irradiating cells with an 800 nm laser. Evidence here shown supports the potential application of the biodegradable photoresponsive NPs in the clinical stage due to the biocompatibility of the materials used, the spatiotemporal control of the therapy and, also, the less likely development of resistance against the combinatorial therapy.

The -174G>C and -596G>A Polymorphisms Are Not Associated with Circulating IL-6 Levels in Breast Cancer Patients from Jalisco, México.

Introduction: Interleukin-6 (IL-6) is a circulating proinflammatory cytokine that fulfills an important role in the survival and proliferation of cancer cells. Overexpression of IL-6, possibly due to the -174G>C and -596G>A polymorphisms in the IL6 gene, has been shown to be related to breast cancer (BC) and a more aggressive course of the disease. Aim: To determine the influence of the -174G>C and -596G>A polymorphisms of the IL6 gene on the circulating levels of IL-6 in BC patients from Jalisco, México. Methodology: Genotyping of the two polymorphisms was carried out on 208 BC patients and 219 healthy controls through polymerase chain reaction-restriction fragment length polymorphism analyses. In addition, the plasma IL-6 concentration levels were measured in the BC patients. Results: There was no significant association between BC and the IL-6 alleles and genotypes (-174G>C, p = 0.276; -596G>A, p = 0.762) under study. Similarly, there were no significant differences in the mean plasma IL-6 concentrations associated with the polymorphisms that were analyzed (-174G>C, p = 0.839; -596G>A, p = 0.848). Conclusions: No evidence was found that the analyzed polymorphisms are associated with the IL-6 expression or concentration in patients suffering from BC from Jalisco, Mexico.

Cisplatin-loaded PLGA nanoparticles for HER2 targeted ovarian cancer therapy.

The conventional treatment (cytoreduction combined with cisplatin/carboplatin and taxane drugs) of ovarian cancer has a high rate of failure and recurrence despite a favorable initial response. This lack of success is usually attributed to the development of multidrug resistance mechanisms by cancer cells and avoidance of the anti-growth effects of monoclonal targeted therapeutic antibodies. The disease, like other cancers, is characterized by the overexpression of molecular markers, including HER2 receptors. Preclinical and clinical studies with trastuzumab, a HER2-targeted therapeutic antibody, reveal a low improvement of the outcomes of HER2 positive ovarian cancer patients. Therefore, here, we propose a cisplatin-loaded, HER2 targeted poly(lactic-co-glycolic) nanoplatform, a system capable to escape the drug-efflux effect and to take advantage of the overexpressed HER2 receptors, using them as docks for targeted chemotherapy. The NP/trastuzumab ratio was determined after fluorescein labeling of antibodies and quantification of fluorescence in NPs. The system was also characterized in terms of size, zeta potential, drug release kinetics, cytotoxicity and cellular internalization in the epithelial ovarian cancer cell line SKOV-3, and compared with the HER2 negative breast cancer cell line HCC70. Our results show an increased cytotoxicity of NPs as compared to free cisplatin, and moreover, an enhanced internalization and cytotoxicity due to the bionfunctionalization of NPs with the monoclonal antibody.

Rational Surface Engineering of Colloidal Drug Delivery Systems for Biological Applications.

The use of colloidal particles as drug delivery carriers holds a great promise in terms of improvement of traditional treatment and diagnosis of human diseases. Nano- and microsized particles of a different composition including organic and inorganic materials can be fabricated with a great control over size, shape and surface properties. Nevertheless, only some few formulations have surpassed the benchtop and reached the bedside. The principal obstacle of colloidal drug delivery systems is their poor accumulation in target tissues, organs and cells, mainly by efficient sequestration and elimination by the mononuclear phagocytic system. Recent evidence suggests that, besides size, the surface character of colloidal systems is the most determinant design parameter that may ultimately guarantee successful biological performance. To approach these issues, materials designers and engineers can make use of multiple strategies and tools to finely modulate the particles' surface towards highly efficient and biocompatible materials. In this article, we provide an overview of the most relevant colloidal drug delivery systems, a summary of the available literature regarding the effects of surface charge, hydrophobicity and softness on biological response, and finally, we review the key points of surface modification strategies with organic, inorganic and biological materials.

Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics.

In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy.

Preparation of PLGA/Rose Bengal colloidal particles by double emulsion and layer-by-layer for breast cancer treatment.

The use of colloidal particles (CPs) in the transport of drugs is developing rapidly thanks to its effectiveness and biosafety, especially in the treatment of various types of cancer. In this study Rose Bengal/PLGA CPs synthesized by double emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were characterized and evaluated as potential breast cancer treatment. CPs were evaluated in terms of size, zeta potential, drug release kinetics and cell viability inhibition efficacy with the triple negative breast cancer cell line HCC70. The results showed that both types of CPs can be an excellent alternative to conventional cancer treatment by taking advantage of the enhanced permeation and retention (EPR) effect, manifested by solid tumors; however, the double emulsion CPs showed more suitable delivery times of up to 60% within two days, while layer-by-layer showed fast release of 50% in 90 min. Both types of CPs were capable to decrease cell viability, which encourage us to further testing in in vivo models to prove their efficacy and feasible use in the treatment of triple negative breast cancer.

Immobilization effects on the photocatalytic activity of CdS quantum Dots-Horseradish peroxidase hybrid nanomaterials.

The potential use of hybrid nanomaterials based on inorganic optically active nanoparticles known as quantum dots (QDs) and horseradish peroxidase (HRP) has been proposed by several authors as light-controllable nanocatalyzers, moreover, the immobilization within or over silica based supports represents an advantage over bulk-dispersed systems. However, the implications of the immobilization of such hybrid photoactivatable catalyzing systems have not been clarified with detail. Here, we present a thorough study of the functional photoactive efficiency and recycling of immobilized CdS QDs and HRP systems with different configurations, immobilized over silanized silica quartz crystal microbalance (QCM) sensors, allowing an accurate measure of the immobilized mass of each component and its correlation with the initial reaction rate of conversion of Amplex Red (AR) to resorufin. As well, the conversion efficiency is compared between the different systems and also to non-immobilized QD-HRP complexed systems.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia.

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Easy and Efficient Cell Tagging with Block Copolymer-Based Contrast Agents for Sensitive MRI Detection in Vivo.

Superparamagnetic iron oxide nanoparticles (MNPs) together with magnetic resonance imaging (MRI) are the preferred tools for monitoring the fate and biodistribution of administered cells in stem cell therapy studies. Commercial MNPs need transfection agents and long incubation times for sufficient cell labeling and further in vivo cell detection. In this work, we have synthesized MNPs coated with pluronic F127 and tetronic 908, and validated their applicability as contrast agents for MRI cell detection on two different cell types: rat mesenchymal stem cells (MSCs) and multipotent neural progenitor cell line from mice (C17.2). No transfection agent was needed for a complete MNP internalization, and the uptake was only dependent on MNP concentration in medium and limited on the incubation time. By combining in vivo MRI and ex vivo histology microscopy, we have demonstrated the MRI signal detected corresponded exclusively to labeled cells and not to free particles. Pluronic F127- and tetronic 908-coated MNPs represent promising contrast agents for stem cell tracking due to their ease of use in preparation, their efficiency for cell labeling, and their high sensitivity for in vivo cell detection.