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Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effective uptake and DOX linked to MNPs was more efficiently retained inside the cells than free DOX, leading to cell inactivation by mitotic catastrophe, senescence and apoptosis. Both effects, uptake and cytotoxicity, were demonstrated by different assays and videomicroscopy techniques. Likewise, covalently functionalized MNPs using three different linkers&mdash, disulfide (DOX-S-S-Pyr, called MF66-S-S-DOX), imine (DOX-I-Mal, called MF66-I-DOX) or both (DOX-I-S-S-Pyr, called MF66-S-S-I-DOX)&mdash, were also analysed. The highest cell death was detected using a linker sensitive to both pH and reducing environment (DOX-I-S-S-Pyr). The greatest success of this study was to detect also their activity against breast cancer stem-like cells (CSC) from MDA-MB-231 and primary breast cancer cells derived from a patient with a similar genetic profile (triple-negative breast cancer). In summary, these nanoformulations are promising tools as therapeutic agent vehicles, due to their ability to produce efficient internalization, drug delivery, and cancer cell inactivation, even in cancer stem-like cells (CSCs) from patients.

© The Author(s)., Controlled delivery of multiple chemotherapeutics can improve the effectiveness of treatments and reduce side effects and relapses. Here in, we used albumin-stabilized gold nanoclusters modified with doxorubicin and SN38 (AuNCs-DS) as combined therapy for cancer. The chemotherapeutics are conjugated to the nanostructures using linkers that release them when exposed to different internal stimuli (Glutathione and pH). This system has shown potent antitumor activity against breast and pancreatic cancer cells. Our studies indicate that the antineoplastic activity observed may be related to the reinforced DNA damage generated by the combination of the drugs. Moreover, this system presented antineoplastic activity against mammospheres, a culturing model for cancer stem cells, leading to an efficient reduction of the number of oncospheres and their size. In summary, the nanostructures reported here are promising carriers for combination therapy against cancer and particularly to cancer stem cells., his research was funded by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78454-C2-2-R, SAF2014-56763-R, and SAF2017-87305-R), Comunidad de Madrid (S2013/MIT-2850), Asociación Española Contra el Cáncer, and IMDEA Nanociencia IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686).

We have performed a series of in vitro tests proposed for the reliable assessment of safety associated with nanoparticles-cell interaction. A thorough analysis of toxicity of three different coating iron oxide nanoparticles on HeLa cells has been carried out including, methyl thiazol tetrazolium bromide (MTT) and Trypan blue exclusion tests, cell morphology observation by optical and Scanning Electron Microscopy (SEM), study of cytoskeletal components, analysis of cell cycle and the presence of reactive oxygen species (ROS). We have quantified magnetic nanoparticle internalization, determined possible indirect cell damages and related it to the nanoparticle coating. The results confirm a very low toxicity of the analyzed iron oxide nanoparticles into HeLa cells by multiple assays and pave the way for a more successful cancer diagnostic and treatment without secondary effects. From the Clinical Editor: In this paper, three different iron oxide nanoparticles are studied and compared from the standpoint of safety and toxicity in HeLa cells, demonstrating low toxicity for each preparation, and paving the way to potential future clinical applications. © 2014 Elsevier Inc., This work was partially supported by grants from Spanish Ministry of Economy and Competitiveness (CTQ2010-20870-C03-03 and MAT2011-23641), Madrid regional government CM (S009/MAT-1726) and EU-FP7 MULTIFUN project (nº 262943). LG holds a Sara Borrell postdoctoral contract (CD09/00030) from ISCIII-MSPS.

Introduction Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles which display a high heating potential and are functionalized with a cell internalization and a chemotherapeutic agent to increase cell death. Methods The superparamagnetic iron oxide nanoparticles (MF66) were electrostatically functionalized with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231. Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female athymic nude mice. Results All nanoparticle variants showed an excellent heating potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions: H = 15.4 kA/m, f = 435 kHz). We could show a gradual inter- and intracellular release of the ligands, and nanoparticle uptake in cells was increased by the N6L functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were more cytotoxic to breast cancer cells than the respective free ligands. We observed a substantial tumor growth inhibition (to 40% of the initial tumor volume, complete tumor regression in many cases) after intratumoral injection of the nanoparticles in vivo. The proliferative activity of the remaining tumor tissue was distinctly reduced. Conclusion The therapeutic effects of breast cancer magnetic hyperthermia could be strongly enhanced by the combination of MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy) and represents a straightforward strategy for translation into the clinical practice when injecting nanoparticles intratumorally. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0576-1) contains supplementary material, which is available to authorized users.

Many therapeutic applications of magnetic nanoparticles involve the local administration of nanometric iron oxide based materials as seeds for magnetothermia or drug carriers. A simple and widespread way of controlling the process using x-ray computed tomography (CT) scanners is desirable. The combination of iron and bismuth in one entity will increase the atenuation of xrays, offering such a possibility. In order to check this possibility core-shell nanocrystals of iron oxide@bismuth oxide have been synthesized by an aqueous route and stabilized in water by polyethylene glycol (PEG), and we have evaluated their ability to generate contrast by CT and magnetic resonance imaging (MRI) to measure the radiopacity and proton relaxivities using phantoms. High-resolution scanning transmission electron microscopy (STEM) revealed that the material consists of a highly crystalline 8 nm core of maghemite and a 1 nm shell of bismuth atoms either isolated or clustered on the nanocrystal's surface. The comparison of μCT and MRI images of mice acquired in the presence of the contrast shows that when local accumulations of the magnetic nanoparticles take place, CT images are more superior in the localization of the magnetic nanoparticles than MRI images, which results in magnetic field inhomogeneity artifacts., This work was supported by the Spanish Ministry of Economy and Competitiveness through Project MAT2011-23641. The authors acknowledge the help of Dr Ruiz Cabello and Dr Herranz in the relaxometric measurements at the Centro Nacional de Investigaciones Cardiovasculares CNIC and acknowledge Guerbet Group for the economic support and the supply of Xenetix®. The research at ORNL US, the Department of Energy (DOE), Basic Energy Sciences (BES), the Materials Sciences and Energy Division (MV) and the Complutense University of Madrid (UCM) was supported by the ERC Starting Investigator Award STEMOX 739239.