MESOSCALE ASSEMBLIES OF INORGANIC NANOPARTICLES FOR THERANOSTIC APPLICATIONS

During the three years of my Ph.D, Ph.D cycle XXXII (2016-2019), at the Fondazione Istituto Italiano di Tecnologia, under the supervision of Dr.Teresa Pellegrino and the co-supervision of Prof.Orietta Monticelli (University of Genova), my focus was mainly on developing colloidally stable nanoclusters assembled at well-defined geometries produced from benchmark iron oxide nanocubes. These nanoclusters were designed, exploited and characterized for their potential use in theranostic applications comprising their exploitation in Magnetic Hyperthermia, Magnetic Resonance Imaging (MRI) and Magnetic Nanoparticles Imaging. As the first aim, my focus was on building a two-dimensional nanoplatform based on highly efficient iron oxide nanocubes enwrapped with a bacteria extracted, biodegradable and biocompatible polyhydroxyalkanoate copolymer. Moreover, these magnetic polymeric clusters exhibit the unique feature to disassemble upon exposure to an intracellular rich lytic enzyme solution thus providing a gradual change in the cluster configuration accompanied by a gradual increase of magnetic heat performances in comparison to the initial 2D-clusters and to the individual iron oxide nanocubes used as building blocks for the cluster preparation. Indeed, comparing magnetic heat properties of the 2D assemblies with three dimensional centro-symmetrical assemblies (3D-MNBs) or single iron oxide nanocubes from same batch of cubes, emphasize how the initial 2D-assembly of iron oxide nanocubes s (2D-MNBs) dispersed in water are more advanced than the 3D-assemblies, but worse with respect to individual nanocubes. In addition, the heat abilities of these 2D clusters progressively increased when incubated in presence of esterase enzyme under physiological temperature, after 3 hours of incubation the specific absorption rate values, a measure of the heat-ability of the nanoparticles under a radio frequency were almost double than that of single cubes. Such an increase corresponds to disassembling of 2D-MNBs into short chain-like clusters of few nanocubes. Remarkably, our 2D-MNBs did not exhibit any variations in heat performance even after inducing an intentional aggregation. This is not the case for individual nanocubes. Magnetophoresis measurements suggest a faster response of 3D and 2D clusters to external magnets (0.3T) than that of individual nanocubes. This feature is desirable for the physical accumulation of magnetic materials under external magnetic field gradients. To the best of our knowledge, this is the first example of a nanoplatform, which combined enzymatic cleavable properties to a clear enhancement of the magnetic heat losses. In addition to this cluster study, I have also contributed to characterize other chain-like assemblies, named Dimer/Trimer obtained by assembling low interacting core-shell of wustite/magnetite iron oxide nanocubes into an amphiphilic copolymer, poly(styrene-co-maleic anhydride) cumene-terminated. Interestingly, by modulating the amount of polymer to nanoparticle surface ratio, the geometry of the same clusters could be modulated from a single structure to Dimer/Trimer to centrosymmetric structures. The short chains of nanocubes exhibit even in this case an enhanced specific absorption rate value with respect to single cubes and centrosymmetric clusters. Overall these studies reveal the significance of particle arrangement as a means to improve magnetic heating performances of the same building blocks, the nanocubes in our case. According to our second aim, the above nanoclusters (developed for magnetic hyperthermia mentioned) were investigated as magnetic tracers, to unveil their diagnostic features for, recently emerging magnetic nanoparticles imaging (MPI) and for Magnetic resonance imaging (MRI). The multimodal imaging models with combined MPI and MRI properties could assist in real-time mapping of tissues that expected to improve the diagnostic accuracy. We found that the 2D-MNBs based on high interacting Iron oxide nanocubes exhibit poor MPI signal than that of standard Resovist. However, this signal of 2D-MNBs underwent a progressive increase upon incubation with esterase enzyme under physiological temperature (almost doubled) starting from their initial state, which attributes to the splitting of 2D beads into a small chain-like configuration. These results show a similar trend to the enzymatic triggered increase in heat performance, as mentioned above. Moreover, the 2D-MNBs possess a remarkable transverse relaxation rate (r2), indicating an efficient negative contrast of 2D-MNBs as agents for MRI. This value reduced by half upon exposure to lytic enzyme providing a significant T2-signal change upon to a stimulus triggered change (the enzymatic degradation). On the other side, among the nanoclusters based on core-shell iron oxide nanocubes; single structure, Dimer/Trimer to centrosymmetric structures, Dimer/Trimer exhibit a very remarkable MPI signal in comparison to the nanocube assemblies and to the individual nanoparticles and with respect to Resovist the most accepted FDA approved standard. Complementing the signal dominance in short chains of 2D-MNBs, the increase of MPI signal in Dimer/Trimer can also corresponds to their short uniaxial configuration. In addition, they have given a very significant transverse relaxation rate (r2) than many other superparamagnetic iron oxide nanoparticles. This kind of nanovectors with multifunctional theranostic features of MRI, MPI and magnetic hyperthermia are beneficial to improve thermo-therapy treatment of cancerous tissues while offering at the same time a potential readable and changing signal for image mapping. Finally, as reported in chapter 3, we aim to develop an assembled nanoplatform made of magnetic iron oxide nanocube-based clusters and gadolinium-based nanoparticles that make the assembly responsive to the tumor microenvironment. This will enable to track tumor accumulation and disassembly of the nanoplatform for efficient thermotherapy based on T1 gadolinium-changing signal. For this purpose, we synthesize multicomponent nanostructures starting from iron oxide nanocubes embedded in a polymeric bead (MNBs) with a surface negative charge and decorated with Sodium gadolinium fluoride nanoparticles (NaGdF4 NPs), placed in between enzyme-degradable polymer spacers. Our hybrid structure achieved desired heating abilities under an alternative magnetic field of biological relevance. In addition to prominent T2 properties coming from MNBs, we demonstrated disassembling and detaching of polymer and NaGdF4 NPs from the surface of the MNBs upon exposure to enzymes that in turn improved water accessibility to NaGdF4 NP surface with a corresponding increase of T1 signal. In this way, we tracked the morphological changes of the systems at different time points of incubation in the presence of an enzyme, by MRI changing signal. This data was also confirmed by observing structural changes using TEM imaging. The integration of diagnostic tools to benchmark therapeutic probes could be a smart approach that enables to track the nanoparticle accumulation through artifact-free diagnosis and improve the heat efficiency of the magnetic hyperthermia treatment at the tumor

Temperature-dependent magnetic particle imaging with multi-harmonic lock-in detection

Advances in instrumentation and tracer materials are still required to enable sensitive and accurate 3D temperature monitoring by magnetic particle imaging. We have developed a magnetic particle imaging instrument to observe temperature variations using MPI, and discuss resolution dependence on temperature and harmonic number. Furthermore, we present a low noise approach using lock-in detection for temperature measurement, and discuss implications for a new detection modality of MPI.Comment: 26 pages, 17 figure

Partial aggregation for collective communication in distributed memory machines

High Performance Computing (HPC) systems interconnect a large number of Processing Elements (PEs) in high-bandwidth networks to simulate complex scientific problems. The increasing scale of HPC systems poses great challenges on algorithm designers. As the average distance between PEs increases, data movement across hierarchical memory subsystems introduces high latency. Minimizing latency is particularly challenging in collective communications, where many PEs may interact in complex communication patterns. Although collective communications can be optimized for network-level parallelism, occasional synchronization delays due to dependencies in the communication pattern degrade application performance. To reduce the performance impact of communication and synchronization costs, parallel algorithms are designed with sophisticated latency hiding techniques. The principle is to interleave computation with asynchronous communication, which increases the overall occupancy of compute cores. However, collective communication primitives abstract parallelism which limits the integration of latency hiding techniques. Approaches to work around these limitations either modify the algorithmic structure of application codes, or replace collective primitives with verbose low-level communication calls. While these approaches give fine-grained control for latency hiding, implementing collective communication algorithms is challenging and requires expertise knowledge about HPC network topologies. A collective communication pattern is commonly described as a Directed Acyclic Graph (DAG) where a set of PEs, represented as vertices, resolve data dependencies through communication along the edges. Our approach improves latency hiding in collective communication through partial aggregation. Based on mathematical rules of binary operations and homomorphism, we expose data parallelism in a respective DAG to overlap computation with communication. The proposed concepts are implemented and evaluated with a subset of collective primitives in the Message Passing Interface (MPI), an established communication standard in scientific computing. An experimental analysis with communication-bound microbenchmarks shows considerable performance benefits for the evaluated collective primitives. A detailed case study with a large-scale distributed sort algorithm demonstrates, how partial aggregation significantly improves performance in data-intensive scenarios. Besides better latency hiding capabilities with collective communication primitives, our approach enables further optimizations of their implementations within MPI libraries. The vast amount of asynchronous programming models, which are actively studied in the HPC community, benefit from partial aggregation in collective communication patterns. Future work can utilize partial aggregation to improve the interaction of MPI collectives with acclerator architectures, and to design more efficient communication algorithms

Uncovering the magnetic particle imaging and magnetic resonance imaging features of iron oxide nanocube clusters

Multifunctional imaging nanoprobes continue to garner strong interest for their great potential in the detection and monitoring of cancer. In this study, we investigate a series of spatially arranged iron oxide nanocube-based clusters (i.e., chain-like dimer/trimer, centrosymmetric clusters, and enzymatically cleavable two-dimensional clusters) as magnetic particle imaging and magnetic resonance imaging probes. Our findings demonstrate that the short nanocube chain assemblies exhibit remarkable magnetic particle imaging signal enhancement with respect to the individually dispersed or the centrosymmetric cluster analogues. This result can be attributed to the beneficial uniaxial magnetic dipolar coupling occurring in the chain-like nanocube assembly. Moreover, we could effectively synthesize enzymatically cleavable two-dimensional nanocube clusters, which upon exposure to a lytic enzyme, exhibit a progressive increase in magnetic particle imaging signal at well-defined incubation time points. The increase in magnetic particle imaging signal can be used to trace the disassembly of the large planar clusters into smaller nanocube chains by enzymatic polymer degradation. These studies demonstrate that chain-like assemblies of iron oxide nanocubes offer the best spatial arrangement to improve magnetic particle imaging signals. In addition, the nanocube clusters synthesized in this study also show remarkable transverse magnetic resonance imaging relaxation signals. These nanoprobes, previously showcased for their outstanding heat performance in magnetic hyperthermia applications, have great potential as dual imaging probes and could be employed to improve the tumor thermo-therapeutic efficacy, while offering a readable magnetic signal for image mapping of material disassemblies at tumor sites

Real-time 3D human body pose estimation from monocular RGB input

Human motion capture finds extensive application in movies, games, sports and biomechanical analysis. However, existing motion capture solutions require cumbersome external and/or on-body instrumentation, or use active sensors with limits on the possible capture volume dictated by power consumption. The ubiquity and ease of deployment of RGB cameras makes monocular RGB based human motion capture an extremely useful problem to solve, which would lower the barrier-to entry for content creators to employ motion capture tools, and enable newer applications of human motion capture. This thesis demonstrates the first real-time monocular RGB based motion-capture solutions that work in general scene settings. They are based on developing neural network based approaches to address the ill-posed problem of estimating 3D human pose from a single RGB image, in combination with model based fitting. In particular, the contributions of this work make advances towards three key aspects of real-time monocular RGB based motion capture, namely speed, accuracy, and the ability to work for general scenes. New training datasets are proposed, for single-person and multi-person scenarios, which, together with the proposed transfer learning based training pipeline, allow learning based approaches to be appearance invariant. The training datasets are accompanied by evaluation benchmarks with multiple avenues of fine-grained evaluation. The evaluation benchmarks differ visually from the training datasets, so as to promote efforts towards solutions that generalize to in-the-wild scenes. The proposed task formulations for the single-person and multi-person case allow higher accuracy, and incorporate additional qualities such as occlusion robustness, that are helpful in the context of a full motion capture solution. The multi-person formulations are designed to have a nearly constant inference time regardless of the number of subjects in the scene, and combined with contributions towards fast neural network inference, enable real-time 3D pose estimation for multiple subjects. Combining the proposed learning-based approaches with a model-based kinematic skeleton fitting step provides temporally stable joint angle estimates, which can be readily employed for driving virtual characters.Menschlicher Motion Capture findet umfangreiche Anwendung in Filmen, Spielen, Sport und biomechanischen Analysen. Bestehende Motion-Capture-Lösungen erfordern jedoch umständliche externe Instrumentierung und / oder Instrumentierung am Körper, oder verwenden aktive Sensoren deren begrenztes Erfassungsvolumen durch den Stromverbrauch begrenzt wird. Die Allgegenwart und einfache Bereitstellung von RGB-Kameras macht die monokulare RGB-basierte Motion Capture zu einem äußerst nützlichen Problem. Dies würde die Eintrittsbarriere für Inhaltsersteller für die Verwendung der Motion Capture verringern und neuere Anwendungen dieser Tools zur Analyse menschlicher Bewegungen ermöglichen. Diese Arbeit zeigt die ersten monokularen RGB-basierten Motion-Capture-Lösungen in Echtzeit, die in allgemeinen Szeneneinstellungen funktionieren. Sie basieren auf der Entwicklung neuronaler netzwerkbasierter Ansätze, um das schlecht gestellte Problem der Schätzung der menschlichen 3D-Pose aus einem einzelnen RGB-Bild in Kombination mit einer modellbasierten Anpassung anzugehen. Insbesondere machen die Beiträge dieser Arbeit Fortschritte in Richtung drei Schlüsselaspekte der monokularen RGB-basierten Echtzeit-Bewegungserfassung, nämlich Geschwindigkeit, Genauigkeit und die Fähigkeit, für allgemeine Szenen zu arbeiten. Es werden neue Trainingsdatensätze für Einzel- und Mehrpersonen-Szenarien vorgeschlagen, die zusammen mit der vorgeschlagenen Trainingspipeline, die auf Transferlernen basiert, ermöglichen, dass lernbasierte Ansätze nicht von Unterschieden im Erscheinungsbild des Bildes beeinflusst werden. Die Trainingsdatensätze werden von Bewertungsbenchmarks mit mehreren Möglichkeiten einer feinkörnigen Bewertung begleitet. Die angegebenen Benchmarks unterscheiden sich visuell von den Trainingsaufzeichnungen, um die Entwicklung von Lösungen zu fördern, die sich auf verschiedene Szenen verallgemeinern lassen. Die vorgeschlagenen Aufgabenformulierungen für den Einzel- und Mehrpersonenfall ermöglichen eine höhere Genauigkeit und enthalten zusätzliche Eigenschaften wie die Robustheit der Okklusion, die im Kontext einer vollständigen Bewegungserfassungslösung hilfreich sind. Die Mehrpersonenformulierungen sind so konzipiert, dass sie unabhängig von der Anzahl der Subjekte in der Szene eine nahezu konstante Inferenzzeit haben. In Kombination mit Beiträgen zur schnellen Inferenz neuronaler Netze ermöglichen sie eine 3D-Posenschätzung in Echtzeit für mehrere Subjekte. Die Kombination der vorgeschlagenen lernbasierten Ansätze mit einem modellbasierten kinematischen Skelettanpassungsschritt liefert zeitlich stabile Gelenkwinkelschätzungen, die leicht zum Ansteuern virtueller Charaktere verwendet werden können

High-Performance Communication Primitives and Data Structures on Message-Passing Manycores:Broadcast and Map

The constant increase in single core frequency reached a plateau during recent years since the produced heat inside the chip cannot be cooled down by existing technologies anymore. An alternative to harvest more computational power per die is to fabricate more number of cores into a single chip. Therefore manycore chips with more than thousand cores are expected by the end of the decade. These environments provide a high level of parallel processing power while their energy consumption is considerably lower than their multi-chip counterparts. Although shared-memory programming is the classical paradigm to program these environments, there are numerous claims that taking into account the full life cycle of software, the message-passing programming model have numerous advantages. The direct architectural consequence of applying a message-passing programming model is to support message passing between the processing entities directly in the hardware. Therefore manycore architectures with hardware support for message passing are becoming more and more visible. These platforms can be seen in two ways: (i) as a High Performance Computing (HPC) cluster programmed by highly trained scientists using Message Passing Interface (MPI) libraries; or (ii) as a mainstream computing platform requiring a global operating system to abstract away the architectural complexities from the ordinary programmer. In the first view, performance of communication primitives is an important bottleneck for MPI applications. In the second view, kernel data structures have been shown to be a limiting factor. In this thesis (i) we overview existing state-of-the-art techniques to circumvent the mentioned bottlenecks; and (ii) we study high-performance broadcast communication primitive and map data structure on modern manycore architectures, with message-passing support in hardware, in two different chapters respectively. In one chapter, we study how to make use of the hardware features to implement an efficient broadcast primitive. We consider the Intel Single-chip Cloud Computer (SCC) as our target platform which offers the ability to move data between on-chip Message Passing Buffers (MPB) using Remote Memory Access (RMA). We propose OC-Bcast (On-Chip Broadcast), a pipelined k-ary tree algorithm tailored to exploit the parallelism provided by on-chip RMA. Experimental results show that OC-Bcast attains considerably better performance in terms of latency and throughput compared to state-of-the-art solutions. This performance improvement highlights the benefits of exploiting hardware features of the target platform: Our broadcast algorithm takes direct advantage of RMA, unlike the other broadcast solutions which are based on a higher-level send/receive interface. In the other chapter, we study the implementation of high-throughput concurrent maps in message-passing manycores. Partitioning and replication are the two approaches to achieve high throughput in a message-passing system. This chapter presents and compares different strongly-consistent map algorithms based on partitioning and replication. To assess the performance of these algorithms independently of architecture-specific features, we propose a communication model of message-passing manycores to express the throughput of each algorithm. The model is validated through experiments on a 36-core TILE-Gx8036 processor. Evaluations show that replication outperforms partitioning only in a narrow domain

Zn- A nd (Mn, Zn)-substituted versus unsubstituted magnetite nanoparticles: Structural, magnetic and hyperthermic properties

In this work, we studied structural and magnetic properties of 18 nm sized Zn-substituted magnetite, 28 nm sized unsubstituted and 17 nm sized (Mn, Zn)-substituted iron oxide nanoparticles, synthesized by thermal decomposition method. Their features were examined by analyzing the X-ray diffraction data, 57Fe Mössbauer spectra and magnetization measurements by SQUID interferometer. The microstructure was inspected comparing the different size and strain broadening models incorporated into Fullprof software. In terms of crystallinity and size dispersion, applied synthesis protocol shows superiority over decomposition of iron oleate and the co-precipitation synthesis route. The saturation magnetization at T = 5 K was found to be within the M S = 91.2-98.6 A m2kg-1 range, while at 300 K M S of pure and Zn-substituted Fe3O4 nanoparticles is 83.6 and 86.2 A m2kg-1, respectively. Effective magnetic anisotropy constant K eff, estimated under slow measurements by SQUID, is below 20 kJ m-3 in all three samples. Some preliminary measurements of the magnetic hyperthermia performance, expressed via specific absorption rate value showed that the best heating performances were displayed by 18 nm sized oleic acid-coated Zn0.13Fe2.87O4 cubo-octahedrons with SAR ≅ 425 W/gFe at H 0 = 20 kA m-1 and f = 228 kHz.Fil: Jović Orsini, Nataša. University of Belgrade; SerbiaFil: Milić, Mirjana. University of Belgrade; SerbiaFil: Torres Molina, Teobaldo Enrique. Universidad de Zaragoza. Instituto de Nanociencia de Aragón; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin

Multi-materials nano-heterostructures for combined therapy and diagnosis

openThe present dissertation is resulting from the work performed during the Ph.D. research activity carried out at the Italian Institute of Technology (IIT) under the supervision of Dr. Teresa Pellegrino (Nanomaterials for biomedical research line) of the Italian Institute of Technology and Fabio Canepa of the University of Genova. The thesis has been conducted in the framework of the ERC-founded project ICARO (ERC starting grant n° 678109, Principal Investigator: Dr. Teresa Pellegrino), whose main purpose is the development of novel inorganic nanostructures for radiotherapy and chemotherapy of cancer. Thus, this thesis aims to progress the field of nanomedicine. In particular, the first goal of this work is to synthesize innovative water stable chalcogenide nanoparticles, with the purpose of achieving nano-sized platforms capable of incorporating radioactive 64Cu ions, which would make such systems suitable for the use in radiotherapy and for positron emission tomography. The second goal is to explore the coupling of such chalcogenide nanocrystals with magnetic nanoparticles, which are already part of the nanoparticles’ portfolio available in the research group where this thesis was carried out. These nanoparticles have shown great potential for magnetic hyperthermia treatment of cancer and, in combination with radiotherapy, could result in a synergic and more effective cancer treatment. Thus, this thesis provides new ground in the rational design of multifunctional nano-heterostructures for cancer diagnosis and therapy. The first chapter of this thesis deals with the synthesis, water transfer and radiolabeling of ZnS nanoparticles. A non-hydrolitycal thermal decomposition synthesis route was exploited in order to obtain quasi-spherical nanoparticles. Such nanoparticles have hydrophobic ligands on their surface and thus are stable in organic solvents. In order to successfully transfer them to water phase, the ligands were exchanged through a procedure that employs a multi-dentate amphiphilic polymer (cysteamine-poly(isobutylene-alt-maleic anhydride)-polyethylene glycol, CYS-PIMA-PEG), which resulted in inorganic colloids with perfect stability in aqueous phase. On this system, cation exchange reactions with both radioactive and non-radioactive copper were carried out. The optimized protocol for the radiolabeling of ZnS nanocrystals with 64Cu permitted to obtain high values of radiochemical yield (93%), defined as the percentage of the total activity used that is incorporated in the crystals, without losing colloidal stability during radiolabeling reaction or subsequent concentration and purification process. The results obtained indicate ZnS nanoparticles as an efficient nano-platform for the use in radiotherapy and positron emission tomography, given the fast, reproducible and easily clinical-translatable radiolabeling procedure resulting in quantitative incorporation of 64Cu ions. In the second chapter we report the research activity carried out to couple in a single nano-heterostructure, the ZnS nanoparticles or copper-deficient copper sulfide nanoparticles (previously reported to be exploitable as radioisotopes carriers) with highly performing magnetic nanoparticles (iron oxide nanocubes, IONCs) or nano-heterostructures (gold-iron oxide dimers, Au@FeOy). Although the direct growth of ZnS domains on IONCs, through colloidal two-pot seeded-growth synthesis procedures, was not possible, this thesis succeeds on merging the different nanoparticles in a single nano-platform by exploiting the use of gold NPs as “linkers” between magnetic iron oxide domains and copper deficient Cu2-xS domains, using Au@FeOy dimers as seeds for the growth of copper sulfide domains. Thus, this procedure resulted in the production of FeOy@Au@Cu2-xS2 trimers, with the additional possibility to tune the size of the Cu2-xS domain by changing precursors’ concentration. These trimers were thoroughly characterized through diverse structural and magnetic analysis techniques (transition electron microscopy, X-ray diffraction, SQUID magnetometry and UV-VIS-NIR spectroscopy). In particular, magnetic properties measurements, allowed to conclude that the magnetic properties of the FeOy@Au@Cu2-xS trimers are comparable to the ones of the Au@FeOy dimers (used as seeds for the subsequent reaction of growth of Cu2-xS domain). In addition, the trimers display two localized surface plasmon resonance absorption bands, one assigned to the gold domain and the other assignable to the copper deficient copper sulfide domain, respectively localized in the first and second NIR biological windows and, consequently, exploitable in photothermal therapy. In the third chapter, the newly synthesized trimers were transferred to water phase and tested for the application as carriers for 64Cu and as heating probes in magnetic hyperthermia and photothermal therapy. Different strategies were explored in order to develop a reproducible and high-yield water transfer protocol. Among them, a two-step ligand exchange procedure employing methoxy-poly(ethylene glycol)-thiol and poly(catechol)-poly(ethylene glycol) as amphiphilic ligands resulted in aqueous phase stable trimers with high water transfer procedure yield (> 80 %). FeOy@Au@Cu2-xS trimers were also successfully transferred to water, although with lower yields if compared to previous procedure, using a polymer coating procedure and employing commercially available and cost-effective poly-(maleic anhydride-alt-1-octadecene). Lastly, the developed nano-platform showed great relevance in the field of nanomedicine. Indeed, when employed in magnetic hyperthermia, trimers resulted in high SAR values, preserving the excellent hyperthermia performances of the Au@FeOy used as seeds for their synthesis and thus in line with the best magnetic nano-heterostructures reported so far. Radiolabeling reactions were performed on trimers, resulting in a radiochemical yield of 97 %, higher than any value reported so far for 64Cu incorporation in water stable nanocrystals. Furthermore, the stability of the trimers during the radiolabeling and subsequent purification procedures was likewise ensured by the use of CYS-PIMA-PEG as stabilizing agent, permitting to recover quantitatively the nanocrystals and the associated radioactivity. The performances of FeOy@Au@Cu2-xS trimers when used in photothermal heating were also tested under the exposure to 808 nm laser irradiation. Although when using high power density (4.67 W/cm2), a temperature increase of 33°C in five minutes was registered, the performances obtained with lower laser’s power density were limited. However, the possibility to tune the absorption wavelengths by means of changing gold and copper sulfide domain’s properties, gives space to further improvements for these multifunctional nano-heterostructures. To the best of our knowledge, the here described FeOy@Au@Cu2-xS trimers are the first ever reported nano-heterostructures able to combine in one single nano-object the possibility to perform magnetic hyperthermia, photothermal therapy and radiotherapy/positron emission tomography, thus allowing the possible development of more efficient cancer treatments.embargoed_20210319XXXII CICLO - SCIENZE E TECNOLOGIE DELLA CHIMICA E DEI MATERIALI - NanochemistryPELLEGRINO, TERESAFiorito, Sergi