BUSCADOR RECOLECTA

Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy.

Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields. The precise structure, organization, distribution, and density of gold nanoparticles (AuNPs) confined within intracellular compartments such as lysosomes have not been studied comprehensively, hampering the derivation of predictive models of their therapeutic activity within the cells of interest. By using transmission electron microscopy and small-angle X-ray scattering, we have determined that canonical spherical citrate-coated AuNPs in the 3–30 nm size range form fractal clusters in endolysosomes of macrophages, endothelial cells, and colon cancer cells. Statistical analysis revealed that the cluster size and endolysosome size are correlated but do not depend on the size of AuNPs unless larger preformed aggregates of AuNPs are internalized. Smaller AuNPs are confined in greater numbers in loose aggregates covering a higher fraction of the endolysosomes compared to the largest AuNPs. The fractal dimensions of intracellular clusters increased with the particle size, regardless of the cell type. We thus analyzed how these intracellular structure parameters of AuNPs affect their optical absorption and photothermal properties. We observed that a 2nd plasmon resonance band was shifted to the near-infrared region when the nanoparticle size and fractal dimensions of the intracellular cluster increased. This phenomenon of intracellular plasmon coupling is not directly correlated to the size of the intralysosomal cluster or the number of AuNPs per cluster but rather to the compacity of the cluster and the size of the individual AuNPs. The intracellular plasmon-coupling phenomenon translates to an efficient heating efficiency with the excitation of the three cell types at 808 nm, transforming the NIR-transparent canonical AuNPs with sizes below 30 nm into NIR-absorbing clusters in the tumor microenvironment. Harnessing the spontaneous clustering of spherical AuNPs by cells might be a more valuable strategy for theranostic purposes than deploying complex engineering to derive NIR-absorbent nanostructures out of their environment. Our paper sheds light on AuNP intracellular reorganization and proposes a general method to link their intracellular fates to their in situ physical properties exploited in medical applications., This work has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795 and 801305. The authors thank the ANR CarGold-16-CE09-026, ANR Coligomere-18-CE06-0006 and ANR CycLys-18-CE09-0015-01. VMA received a Post-doc fellowship from Association pour le Recherche contre le Cancer (ARC, Aides Individuelles, post-doctorant, dossier 20150603405). ANB received a PhD fellowship by the Institute thematique multi-organismes (ITMO) Cancer and the doctoral school Frontières du Vivant (FdV) – Programme Bettencourt. AB received a PhD fellowship by the doctoral school Physique en Ile de France (EDPIF). This work was supported by the ITMO-Inserm Plan Cancer 2014-2019.

© 2020 by the authors., There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future., The described work was carried out within the project “Multifunctional Nanoparticles for the Selective Detection and Treatment of Cancer” (Multifun), funded by the European Commission (Nr. 262943) and in parts by the European Union’s Horizon 2020 research and innovation program under grant agreement No 685795 and the Spanish Ministry of Economy and Competitiveness (SAF2017-87305-R). IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686).

Iron oxide nanoparticles (IONPs) are well-known contrast agents for MRI for a wide range of sizes and shapes. Their use as theranostic agents requires a better understanding of their magnetic hyperthermia properties and also the design of a biocompatible coating ensuring their stealth and a good biodistribution to allow targeting of specific diseases. Here, biocompatible IONPs of two different shapes (spherical and octopod) were designed and tested in vitro and in vivo to evaluate their abilities as high-end theranostic agents. IONPs featured a dendron coating that was shown to provide anti-fouling properties and a small hydrodynamic size favoring an in vivo circulation of the dendronized IONPs. While dendronized nanospheres of about 22 nm size revealed good combined theranostic properties (r2 = 303 mM s−1, SAR = 395 W gFe−1), octopods with a mean size of 18 nm displayed unprecedented characteristics to simultaneously act as MRI contrast agents and magnetic hyperthermia agents (r2 = 405 mM s−1, SAR = 950 W gFe−1). The extensive structural and magnetic characterization of the two dendronized IONPs reveals clear shape, surface and defect effects explaining their high performance. The octopods seem to induce unusual surface effects evidenced by different characterization techniques while the nanospheres show high internal defects favoring Néel relaxation for magnetic hyperthermia. The study of octopods with different sizes showed that Néel relaxation dominates at sizes below 20 nm while the Brownian one occurs at higher sizes. In vitro experiments demonstrated that the magnetic heating capability of octopods occurs especially at low frequencies. The coupling of a small amount of glucose on dendronized octopods succeeded in internalizing them and showing an effect of MH on tumor growth. All measurements evidenced a particular signature of octopods, which is attributed to higher anisotropy, surface effects and/or magnetic field inhomogeneity induced by tips. This approach aiming at an analysis of the structure–property relationships is important to design efficient theranostic nanoparticles., The Region Alsace, France, and the Labex Chimie des Systemes Complexes, University of Strasbourg, France are gratefully acknowledged for the doctoral fellowship to Geoffrey Cotin. This research project was also co-funded by Labex CSC, Alsace contre le cancer, INCA (project PRTK14, THERAMAG 2014-225) and the INTERREG project NANOTRANSMED. The “NANOTRANSMED” project is co-funded by the European Regional Development Fund (ERDF) and by the Swiss Confederation and the Swiss cantons of Aargau, Basel-Landschaft and Basel-Stadt, in the framework of the INTERREG V Upper Rhine program (“Transcending borders with every project”). The authors thank Morgane Rabineau for epifluorescence imaging and Nadia Messaddeq for TEM imaging of cells. The authors thank the Center for Microscopy and Molecular Imaging (CMMI, supported by the European Regional Development Fund and the Walloon Region). This work was supported by the Fond National de la Recherche Scientifique (FNRS), UIAP VII, ARC Programs of the French Community of Belgium and the Walloon region (Gadolymph and Holocancer programs). All the authors acknowledge the COST action TD1402 “RADIOMAG”. D. Ortega and F. J. Teran acknowledge support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686), the Spanish Ministry of Economy and Competitiveness for the NANOLICO project (MAT2017-85617-R), the Spanish Ministry of Science through the NaNoCAR grant PID2020-117544RB-I00, the Ramón y Cajal grant RYC2018-025253-I and Research Networks grant RED2018-102626-T, the HEATOOLS project (BIO2017-84246-C2-1-R), the Comunidad de Madrid for grant NANOMAGCOST (P2018/NMT-4321), DGA for public funding from Fondo Social (grupos DGA), and the European Commission for the funding received through the H2020 “NoCanTher” project (GA No. 685795)., Peer reviewed

Stimuli-responsive nanomaterials are very attractive for biomedical applications. They can be activated through external stimuli or by the physico-chemical conditions present in cells or tissues. Here, we describe the preparation of hybrid iron oxide-manganese oxide core-satellite shell nanostructures that change their contrast mode in magnetic resonance imaging (MRI) from T2 to T1, after being internalized by cells. This occurs by the dissolution of the MnO2 of the shell, preserving intact the iron oxide at the core. First, we study the seeded-growth synthesis of iron oxide-manganese oxide nanoparticles studying the effect of varying the core size of the magnetic seeds and the concentration of the surfactant. This allows tuning the size and shape of the final hybrid nanostructure. Then, we show that the shell can be removed by a redox reaction with glutathione, which is naturally present inside the cells at much higher concentrations than outside the cells. Finally, the dissolution of the MnO2 shell and the change in the contrast mode is confirmed in cell cultures. After this process, the iron oxide nanoparticles at the core remain intact and are still active as heating mediators when an alternating magnetic field is applied., This work was supported by the Ministerio de Ciencia e Innovación (PID2019-106301RB-I00 to GS and PGC2018-096016-B-I00 to L.G.), Instituto de Salud Carlos III (PT20/00044; co‐funded by European Union, European Regional Development Fund, ERDF, “A way of making Europe”), Ministerio de Economía y Competitividad (SAF2017-87305-R), Comunidad de Madrid (fellowships PEJD-2016/IND-2293 and IND2017/IND-7809; projects B2017/BMD-3867; P2018/NMT-4321), European Commission H2020 programme (project NOCANTHER, grant agreement no. 685795), and Asociación Española Contra el Cáncer. IMDEA Nanociencia acknowledges support from the 'Severo Ochoa' Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation. L.G. acknowledges financial support from the Ramón y Cajal program (RYC-2014-15512). N. L-G also thanks the Spanish Education Ministry for the funding (FPU18/02323). P. M-R- acknowledges the support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686)., Peer reviewed

Supplementary data to this article can be found online at https://doi.org/10.1016/j.jconrel.2025.113791., Pancreatic ductal adenocarcinoma is a highly aggressive cancer with a low survival rate. Thus, efforts are needed to develop more effective treatments. Herein, we propose utilizing magnetic nanoparticles (MNP) for the concurrent delivery of gemcitabine and miRNA34a mimic to target pancreatic cancer cells. The MNP were functionalized with disulfide bonds to selectively release their cargo inside tumor cells. The incorporation of the miRNA34a mimic increased the sensitivity of cells to gemcitabine, especially in BxPC-3 cells. Additionally, the miRNA34a sequence was modified with locked nucleic acids (LNA) to increase stability. The resulting LNA34a showed a stronger cytotoxic effect when combined with gemcitabine, even in PANC-1 cells, which are resistant to the drug. Notably, the modified MNP exhibited less toxicity than their free counterparts when incubated with HaCaT cells, a model of healthy keratinocytes. Additionally, the combined delivery of miRNA34a mimics and gemcitabine using MNP elicited a synergistic cytotoxic effect against pancreatic cancer cells through magnetic hyperthermia. The intratumoral administration of the modified MNP in subcutaneous xenografts of BxPC-3 cells resulted in a sustained increase in temperature when an alternating magnetic field was applied. Notably, the treatment with the MNP functionalized with GEM and LNA34a led to significant changes in the expression of NOTCH1 and NOTCH2 in the tumor, which are direct targets of miRNA34a, as well as HSP70, which is related to the cellular response to stressors like heat., This work was supported by the Spanish Ministry of Economy and Competitiveness [PID2023-146982OB-I00, PID2020- 119352RB-I00, PID2019-106301RB-I00], Comunidad de Madrid [IND2017/IND-7809; S2017/BMD-3867, IND2020/IND-17517, S2022/BMD-7403 RENIM-CM], Asociación Española Contra el Cáncer [PRYCO223002PEIN], and IMDEA Nanociencia. IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D [MINECO, Grant SEV-2016-0686, CEX2020-001039-S]. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 685795 (NoCanTher) and No 814607 (Safe-n-Medtech). We also acknowledge the European Structural and Investment Fund. Nuria Lafuente-Gómez and Mario Martínez-Mingo thankSpanish Science Ministry [FPU18/02323, FJC2021-048151-I, respectively] for the funding., Peer reviewed

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliber-ately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.

Advanced uses of smartphones are changing lifestyles, and may have a great impact in materials science in the near future. In this work, the use of these devices to develop fast, simple, and cheap methods to characterize magnetic nanoparticle suspensions is tested. A series of dilutions of a wide library of magnetic nanoparticles, composed of iron oxide materials in the range between 3 and 43 nm, with two different shapes and four different coatings is prepared. The colloid color is analyzed using the RGB (red, green, blue) color model. Ratios of these parameters are correlated with the suspension iron concentration and with the nanoparticles average size. A linear relationship between the color (in particular the G/R ratio) and both the colloid iron content and the particles size is found. The link between these parameters allows the development of two new methods to determine either the concentration or the particle size of magnetic nanoparticle suspensions just by acquiring images from suspensions of iron oxide magnetic nanoparticles with a smartphone.

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia., This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02).

Objective To investigate the eddy current heating that occurs in metallic biliary stents during magnetic hyperthermia treatments and to assess whether these implants should continue to be an exclusion criterion for potential patients. Methods Computer simulations were run on stent heating during the hyperthermia treatment of local pancreatic tumors (5-15 mT fields at 300 kHz for 30 min), considering factors such as wire diameter, type of stent alloy, and field orientation. Maxwell's equations were solved numerically in a bile duct model, including the secondary field produced by the stents. The heat exchange problem was solved through a modified version of the Pennes' bioheat equation assuming a temperature dependency of blood perfusion and metabolic heat. Results The choice of alloy has a large impact on the stent heating, preferring those having a lower electrical conductivity. Only for low field intensities (5 mT) and for some of the bile duct tissue layers the produced heating can be considered safe. The orientation of the applied field with respect to the stent wires can give rise to the onset of regions with different heating levels depending on the shape that the stent has finally adopted according to the body's posture. Bile helps to partially dissipate the heat that is generated in the lumen of the bile duct, but not at a sufficient rate. Conclusion The safety of patients with pancreatic cancer wearing metallic biliary stents during magnetic hyperthermia treatments cannot be fully assured under the most common treatment parameters.

Purpose: Bearing partially or fully metallic passive implants represents an exclusion criterion for
patients undergoing a magnetic hyperthermia procedure, but there are no specific studies backing
this restrictive decision. This work assesses how the secondary magnetic field generated at the surface
of two common types of prostheses affects the safety and efficiency of magnetic hyperthermia treatments
of localized tumors. The paper also proposes the combination of a multi-criteria decision analysis
and a graphical representation of calculated data as an initial screening during the preclinical risk
assessment for each patient.
Materials and methods: Heating of a hip joint and a dental implant during the treatment of
prostate, colorectal and head and neck tumors have been assessed considering different external
field conditions and exposure times. The Maxwell equations including the secondary field
produced by metallic prostheses have been solved numerically in a discretized computable
human model. The heat exchange problem has been solved through a modified version of the
Pennes’ bioheat equation assuming a temperature dependency of blood perfusion and metabolic
heat, i.e. thermorregulation. The degree of risk has been assessed using a risk index with
parameters coming from custom graphs plotting the specific absorption rate (SAR) vs temperature
increase, and coefficients derived from a multi-criteria decision analysis performed following
the MACBETH approach.
Results: The comparison of two common biomaterials for passive implants - Ti6Al4V and CoCrMo
- shows that both specific absorption rate (SAR) and local temperature increase are found to be
higher for the hip prosthesis made by Ti6Al4V despite its lower electrical and thermal conductivity.
By tracking the time evolution of temperature upon field application, it has been established
that there is a 30 s delay between the time point for which the thermal equilibrium is reached at
prostheses and tissues. Likewise, damage may appear in those tissues adjacent to the prostheses
at initial stages of treatment, since recommended thermal thresholds are soon surpassed for
higher field intensities. However, it has also been found that under some operational conditions
the typical safety rule of staying below or attain a maximum temperature increase or SAR value
is met.
Conclusion: The current exclusion criterion for implant-bearing patients in magnetic hyperthermia
should be revised, since it may be too restrictive for a range of the typical field conditions used.
Systematic in silico treatment planning using the proposed methodology after a well-focused
diagnostic, This work has been supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No [685795]. The authors acknowledge support from the COST Association through the COST actions `RADIOMAG' [TD1402] and `MyWAVE' [CA17115]. D.O. and I.R.R. acknowledge financial support from the Community of Madrid under Contract No. [PEJD-2017-PRE/IND-3663], from the Error! Hyperlink reference not valid. through the Ramon y Cajal grant [RYC2018-025253-I] and Research Networks [RED2018-102626-Hiroshima], as well as the Ministry of Economy and Competitiveness through the grants [MAT2017-85617R] and the `Severo Ochoa' Program for Centers of Excellence in R&D [SEV-2016-0686]. We gratefully acknowledge the support of NVIDIA Corporation through the GPU Grant Program with the donation of the Quadro P6000 GPU used for this research. D. O. acknowledges support from the Programme for the Promotion and Encouragement of Research and Transfer activities at the University of Cadiz.

This dataset from the publication entitled "Dataset from "In silico assessment of collateral eddy current heating in biocompatible implants subjected to magnetic hyperthermia treatments" contains simulated data of magnetic hyperthermia treatments for three different indications: colorectal cancer, prostate cancer and head & neck cancer. Since the aim of the study is to evaluate the risk of thermal damage caused by the collateral heating of two common types of passive prostheses (hip and dental implants), eddy currents induced in these implants upon interacting with the externally applied ac field during treatment have been computed for all the evaluated regions. Two different alloys for the implants have been considered for each case as well: Ti6Al4V and CoCrMo. At the same time, besides temperature, the specific abosorption rate (SAR) have been also computed to work out the energy deposition in tissues.

Calculations have been carried out using a het exchange model with and without thermoregulation.

log-log SAR vs T plots have been obtained and proposed as a quick means to pre-check treatment feasibility in each patient. These graphs are thought to be included in treatment planning prior to the clinical procedure.

Other parameters taken into account have been the treatment time (5 and 30 minutes), and the maximum tolerable temperature threshold (1 or 5 ºC, as indicated by the ICNIRP commission), all for three main types of tissues, namely fat, bone and muscle. Each tissue have been simulated using three different field intensities (5, 10 and 15 mT).

The field frequency has been 300 kHz in all cases.

The files "Dataset_description.doc" and "file_scheme.txt" contain the structure and description of the files that make up the dataset.

UPDATES FROM PREVIOUS VERSIONS: simulations of the dental implant without thermoregulation have been added.