Publications by authors named "Alberto Curcio"

19 Publications

  • Page 1 of 1

Massive Intracellular Remodeling of CuS Nanomaterials Produces Nontoxic Bioengineered Structures with Preserved Photothermal Potential.

ACS Nano 2021 06 25;15(6):9782-9795. Epub 2021 May 25.

Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS and University of Paris, 75205, Paris Cedex 13, France.

Despite efforts in producing nanoparticles with tightly controlled designs and specific physicochemical properties, these can undergo massive nano-bio interactions and bioprocessing upon internalization into cells. These transformations can generate adverse biological outcomes and premature loss of functional efficacy. Hence, understanding the intracellular fate of nanoparticles is a necessary prerequisite for their introduction in medicine. Among nanomaterials devoted to theranostics is copper sulfide (CuS), which provides outstanding optical properties along with easy synthesis and low cost. Herein, we performed a long-term multiscale study on the bioprocessing of hollow CuS nanoparticles (CuS NPs) and rattle-like iron oxide [email protected] core-shell hybrids ([email protected] NPs) when inside stem cells and cancer cells, cultured as spheroids. In the spheroids, both CuS NPs and [email protected] NPs are rapidly dismantled into smaller units (day 0 to 3), and hair-like nanostructures are generated (day 9 to 21). This bioprocessing triggers an adaptation of the cellular metabolism to the internalized metals without impacting cell viability, differentiation, or oxidative stress response. Throughout the remodeling, a loss of IONF-derived magnetism is observed, but, surprisingly, the CuS photothermal potential is preserved, as demonstrated by a full characterization of the photothermal conversion across the bioprocessing process. The maintained photothermal efficiency correlated well with synchrotron X-ray absorption spectroscopy measurements, evidencing a similar chemical phase for Cu but not for Fe over time. These findings evidence that the intracellular bioprocessing of CuS nanoparticles can reshape them into bioengineered nanostructures without reducing the photothermal function and therapeutic potential.
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http://dx.doi.org/10.1021/acsnano.1c00567DOI Listing
June 2021

Iron Oxide Mediated Photothermal Therapy in the Second Biological Window: A Comparative Study between Magnetite/Maghemite Nanospheres and Nanoflowers.

Nanomaterials (Basel) 2020 Aug 7;10(8). Epub 2020 Aug 7.

Laboratoire de PHysico-chimie des Électrolytes et Nanosystèmes InterfaciauX (PHENIX), CNRS UMR8234, Sorbonne Université, F-75252 Paris CEDEX 05, France.

The photothermal use of iron oxide magnetic nanoparticles (NPs) is becoming more and more popular and documented. Herein, we compared the photothermal (PT) therapy potential versus magnetic hyperthermia (MHT) modality of magnetic nanospheres, largely used in the biomedical field and magnetic multicore nanoflowers known among the best nanoheaters. The NPs were imaged using transmission electron microscopy and their optical properties characterized by UV-Vis-NIR-I-II before oxidation (magnetite) and after oxidation to maghemite. The efficiency of all NPs in MHT and PT in the preferred second near-infrared (NIR-II) biological window was carried out in water and in cancer cells. We show that, in water, magnetite nanoflowers are the most efficient nanoheaters for both modalities. Moreover, PT appears much more efficient than MHT at low NP dose, whatever the NP. In the cellular environment, for PT, efficiency was totally conserved, with magnetite nanoflowers as the best performers compared to MHT, which was totally lost. Finally, cell uptake was significantly increased for the nanoflowers compared to the nanospheres. Finally, the antitumor therapy was investigated for all NPs at the same dose delivered to the cancer cells and at reasonable laser power density (0.3 W/cm), which showed almost total cell death for magnetite nanoflowers.
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http://dx.doi.org/10.3390/nano10081548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466508PMC
August 2020

Janus Magnetic-Plasmonic Nanoparticles for Magnetically Guided and Thermally Activated Cancer Therapy.

Small 2020 03 20;16(11):e1904960. Epub 2020 Feb 20.

Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot, 75205, Paris cedex 13, France.

Progress of thermal tumor therapies and their translation into clinical practice are limited by insufficient nanoparticle concentration to release therapeutic heating at the tumor site after systemic administration. Herein, the use of Janus magneto-plasmonic nanoparticles, made of gold nanostars and iron oxide nanospheres, as efficient therapeutic nanoheaters whose on-site delivery can be improved by magnetic targeting, is proposed. Single and combined magneto- and photo-thermal heating properties of Janus nanoparticles render them as compelling heating elements, depending on the nanoparticle dose, magnetic lobe size, and milieu conditions. In cancer cells, a much more effective effect is observed for photothermia compared to magnetic hyperthermia, while combination of the two modalities into a magneto-photothermal treatment results in a synergistic cytotoxic effect in vitro. The high potential of the Janus nanoparticles for magnetic guiding confirms them to be excellent nanostructures for in vivo magnetically enhanced photothermal therapy, leading to efficient tumor growth inhibition.
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http://dx.doi.org/10.1002/smll.201904960DOI Listing
March 2020

Transformation Cycle of Magnetosomes in Human Stem Cells: From Degradation to Biosynthesis of Magnetic Nanoparticles Anew.

ACS Nano 2020 02 16;14(2):1406-1417. Epub 2020 Jan 16.

Laboratoire Matière et Systèmes, Complexes MSC, UMR 7057, CNRS and University of Paris , 75205 , Paris Cedex 13 , France.

The nanoparticles produced by magnetotactic bacteria, called magnetosomes, are made of a magnetite core with high levels of crystallinity surrounded by a lipid bilayer. This organized structure has been developed during the course of evolution of these organisms to adapt to their specific habitat and is assumed to resist degradation and to be able to withstand the demanding biological environment. Herein, we investigated magnetosomes' structural fate upon internalization in human stem cells using magnetic and photothermal measurements, electron microscopy, and X-ray absorption spectroscopy. All measurements first converge to the demonstration that intracellular magnetosomes can experience an important biodegradation, with up to 70% of their initial content degraded, which is associated with the progressive storage of the released iron in the ferritin protein. It correlates with an extensive magnetite to ferrihydrite phase transition. The ionic species delivered by this degradation could then be used by the cells to biosynthesize magnetic nanoparticles anew. In this case, cell magnetism first decreased with magnetosomes being dissolved, but then cells remagnetized entirely, evidencing the neo-synthesis of biogenic magnetic nanoparticles. Bacteria-made biogenic magnetosomes can thus be totally remodeled by human stem cells, into human cells-made magnetic nanoparticles.
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http://dx.doi.org/10.1021/acsnano.9b08061DOI Listing
February 2020

Biological Fate of Magnetic Protein-Specific Molecularly Imprinted Polymers: Toxicity and Degradation.

ACS Appl Mater Interfaces 2019 Oct 19;11(39):35556-35565. Epub 2019 Sep 19.

CNRS, PHysico-chimie des Electrolytes et Nanosystèmes InterfaciauX, PHENIX , Sorbonne Université , F-75005 Paris , France.

Magnetic nanoparticles coated with protein-specific molecularly imprinted polymers (MIPs) are receiving increasing attention thanks to their binding abilities, robustness, and easy synthesis compared to their natural analogues also able to target proteins, such as antibodies or aptamers. Acting as tailor-made recognition systems, protein-specific MIPs can be used in many in vivo nanomedicine applications, such as targeted drug delivery, biosensing, and tissue engineering. Nonetheless, studies on their biocompatibility and long-term fate in biological environments are almost nonexistent, although these questions have to be addressed before considering clinical applications. To alleviate this lack of knowledge, we propose here to monitor the effect of a protein-specific MIP coating on the toxicity and biodegradation of magnetic iron oxide nanoparticles, both in a minimal aqueous degradation medium and in a model of cartilage tissue formed by differentiated human mesenchymal stem cells. Degradation of iron oxide nanoparticles with or without the polymer coating was monitored for a month by following their magnetic properties using vibrating sample magnetometry and their morphology by transmission electron microscopy. We showed that the MIP coating of magnetic iron oxide nanoparticles does not affect their biocompatibility or internalization inside cells. Remarkably, the imprinted polymer coating does not hinder the magnetic particle degradation but seems to slow it down, although this effect is more visible when degradation occurs in the buffer medium than in cells. Hence, the results presented in this paper are really encouraging and open up the way to future applications of MIP-coated nanoparticles into the clinic.
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http://dx.doi.org/10.1021/acsami.9b11717DOI Listing
October 2019

Impact of magnetic nanoparticle surface coating on their long-term intracellular biodegradation in stem cells.

Nanoscale 2019 Sep 27;11(35):16488-16498. Epub 2019 Aug 27.

Laboratoire Matière et Systèmes, Complexes MSC, UMR 7057, CNRS & University Paris Diderot, 75205, Paris Cedex 13, France.

Magnetic nanoparticles (MNPs) internalized within stem cells have paved the way for remote magnetic cell manipulation and imaging in regenerative medicine. A full understanding of their interactions with stem cells and of their fate in the intracellular environment is then required, in particular with respect to their surface coatings. Here, we investigated the biological interactions of MNPs composed of an identical magnetic core but coated with different molecules: phosphonoacetic acid, polyethylene glycol phosphonic carboxylic acid, caffeic acid, citric acid, and polyacrylic acid. These coatings vary in the nature of the chelating function, the number of binding sites, and the presence or absence of a polymer. The nanoparticle magnetism was systematically used as an indicator of their internalization within human stem cells and of their structural long-term biodegradation in a 3D stem cell spheroid model. Overall, we evidence that the coating impacts the aggregation status of the nanoparticles and subsequently their uptake within stem cells, but it has little effect on their intracellular degradation. Only a high number of chelating functions (polyacrylic acid) had a significant protective effect. Interestingly, when the nanoparticles aggregated prior to cellular internalization, less degradation was also observed. Finally, for all coatings, a robust dose-dependent intracellular degradation rate was demonstrated, with higher doses of internalized nanoparticles leading to a lower degradation extent.
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http://dx.doi.org/10.1039/c9nr05624fDOI Listing
September 2019

Iron Oxide Nanoflowers @ CuS Hybrids for Cancer Tri-Therapy: Interplay of Photothermal Therapy, Magnetic Hyperthermia and Photodynamic Therapy.

Theranostics 2019 12;9(5):1288-1302. Epub 2019 Feb 12.

Sorbonne Université, CNRS UMR 8234, Physicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), 4 place Jussieu, 75005 Paris, France.

Innovative synthesis routes revolutionized nanomaterial combination and design possibilities resulting in a new generation of fine-tuned nanoparticles featuring exquisite shape and constitution control. However, there is still room for improvement when it comes to the development of multi-functional nanoparticle agents merging a plurality of therapeutic functions to tackle tumors simultaneously by synergic mechanisms. Herein, we report the design of an optimized nanohybrid for cancer tri-therapy featuring a maghemite (γ-Fe2O3) nanoflower-like multicore nanoparticle conceived for efficient magnetic hyperthermia (MHT) and a spiky copper sulfide shell ([email protected]) with a high near-infrared (NIR) absorption coefficient suitable for photothermal (PTT) and photodynamic therapy (PDT). Spiky-like [email protected] nanohybrids were obtained through a straightforward and scalable water-based template sacrificial synthesis, which allows the shell shape control by tuning polyvinylpyrrolidone (PVP) concentration. A comprehensive characterization of nanohybrid size, shape and structural properties was carried out by combining complementary TEM, SEM, HR-TEM, EELS, XRD and NTA. The all-in-one therapeutic multi-functionality was assessed on cancer cells and on tumor-bearing nude mice. Tests carried out on [email protected] nanohybrid aqueous dispersion demonstrated their impressive efficiency to convert light (conversion coefficient = 42 ± 6 %) and magnetic stimulation (SAR ~ 350 W g) into heat as well as to induce concurrent reactive oxygen species (ROS) formation upon laser irradiation. Such capabilities were further confirmed in cellular environment by tests and at the organism level by tests in a murine tumor model. Notably, complete tumor regression was obtained for the PTT mode at low Cu concentration. Overall, these results allowed determining windows of applicability for each therapy individually or in combination. Altogether, the obtained data evidence the successful synthesis of a unique tri-therapeutic nanoparticle featuring highly relevant assets for clinical translation such as reduced nanoparticle administered dose, reduced laser power exposure, reduced magnetic field frequency, and the possibility of serial heating cycles and therapy monitoring by photoacoustic (PA) and magnetic resonance imaging (MRI). Furthermore, the integration of the dual heating capability (MHT + PTT) with the PDT insult offers a unique asset to tackle tumors by multiple cytotoxic strategies in order to improve the therapeutic outcome in a broader spectrum of clinical conditions.
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http://dx.doi.org/10.7150/thno.30238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401506PMC
January 2020

Biosynthesis of magnetic nanoparticles from nano-degradation products revealed in human stem cells.

Proc Natl Acad Sci U S A 2019 03 13;116(10):4044-4053. Epub 2019 Feb 13.

Laboratoire Matière et Systèmes Complexes, UMR 7057, CNRS and University Paris Diderot, 75205 Paris Cedex 13, France;

While magnetic nanoparticles offer exciting possibilities for stem cell imaging or tissue bioengineering, their long-term intracellular fate remains to be fully documented. Besides, it appears that magnetic nanoparticles can occur naturally in human cells, but their origin and potentially endogenous synthesis still need further understanding. In an effort to explore the life cycle of magnetic nanoparticles, we investigated their transformations upon internalization in mesenchymal stem cells and as a function of the cells' differentiation status (undifferentiated, or undergoing adipogenesis, osteogenesis, and chondrogenesis). Using magnetism as a fingerprint of the transformation process, we evidenced an important degradation of the nanoparticles during chondrogenesis. For the other pathways, stem cells were remarkably "remagnetized" after degradation of nanoparticles. This remagnetization phenomenon is the direct demonstration of a possible neosynthesis of magnetic nanoparticles and could lay some foundation to understand the presence of magnetic crystals in human cells. The neosynthesis was shown to take place within the endosomes and to involve the H-subunit of ferritin. Moreover, it appeared to be the key process to avoid long-term cytotoxicity (impact on differentiation) related to high doses of magnetic nanoparticles within stem cells.
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http://dx.doi.org/10.1073/pnas.1816792116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410821PMC
March 2019

Thermoresponsive Iron Oxide Nanocubes for an Effective Clinical Translation of Magnetic Hyperthermia and Heat-Mediated Chemotherapy.

ACS Appl Mater Interfaces 2019 Feb 1;11(6):5727-5739. Epub 2019 Feb 1.

Istituto Italiano di Tecnologia , via Morego 30 , 16163 Genoa , Italy.

The use of magnetic nanoparticles in oncothermia has been investigated for decades, but an effective combination of magnetic nanoparticles and localized chemotherapy under clinical magnetic hyperthermia (MH) conditions calls for novel platforms. In this study, we have engineered magnetic thermoresponsive iron oxide nanocubes (TR-cubes) to merge MH treatment with heat-mediated drug delivery, having in mind the clinical translation of the nanoplatform. We have chosen iron oxide based nanoparticles with a cubic shape because of their outstanding heat performance under MH clinical conditions, which makes them benchmark agents for MH. Accomplishing a surface-initiated polymerization of strongly interactive nanoparticles such as our iron oxide nanocubes, however, remains the main challenge to overcome. Here, we demonstrate that it is possible to accelerate the growth of a polymer shell on each nanocube by simple irradiation of a copper-mediated polymerization with a ultraviolet light (UV) light, which both speeds up the polymerization and prevents nanocube aggregation. Moreover, we demonstrate herein that these TR-cubes can carry chemotherapeutic doxorubicin (DOXO-loaded-TR-cubes) without compromising their thermoresponsiveness both in vitro and in vivo. In vivo efficacy studies showed complete tumor suppression and the highest survival rate for animals that had been treated with DOXO-loaded-TR-cubes, only when they were exposed to MH. The biodistribution of intravenously injected TR-cubes showed signs of renal clearance within 1 week and complete clearance after 5 months. This biomedical platform works under clinical MH conditions and at a low iron dosage, which will enable the translation of dual MH/heat-mediated chemotherapy, thus overcoming the clinical limitation of MH: i.e., being able to monitor tumor progression post-MH-treatment by magnetic resonance imaging (MRI).
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http://dx.doi.org/10.1021/acsami.8b16226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376448PMC
February 2019

Intracellular Biodegradation of Ag Nanoparticles, Storage in Ferritin, and Protection by a Au Shell for Enhanced Photothermal Therapy.

ACS Nano 2018 07 26;12(7):6523-6535. Epub 2018 Jun 26.

Laboratoire Matière et Systèmes Complexes, UMR 7057 , CNRS and University Paris Diderot , 75205 Paris Cedex 13, France.

Despite their highly efficient plasmonic properties, gold nanoparticles are currently preferred to silver nanoparticles for biomedical applications such as photothermal therapy due to their high chemical stability in the biological environment. To confer protection while preserving their plasmonic properties, we allied the advantages of both materials and produced hybrid nanoparticles made of an anisotropic silver nanoplate core coated with a frame of gold. The efficiency of these hybrid nanoparticles ([email protected]) in photothermia was compared to monometallic silver nanoplates (AgNPs) or gold nanostars (AuNPs). The structural and functional properties of AuNPs, AgNPs, and [email protected] were investigated in environments of increasing complexity, in water suspensions, in cells, and in tumors in vivo. While AgNPs showed the greatest heating efficiency in suspension (followed by [email protected] and AuNPs), this trend was reversed intracellularly within a tissue-mimetic model. In this setup, AgNPs failed to provide consistent photothermal conversion over time, due to structural damage induced by the intracellular environment. Remarkably, the degraded Ag was found to be stored within the iron-storage ferritin protein. By contrast, the Au shell provided the [email protected] with total Ag biopersistence. As a result, photothermal therapy was successful with [email protected] in vivo in a mouse tumor model, providing the ultimate proof on Au shell's capability to shield the Ag core from the harsh biological environment and preserve its excellent heating properties.
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http://dx.doi.org/10.1021/acsnano.8b00482DOI Listing
July 2018

Targeted thermal therapy with genetically engineered magnetite [email protected]: Photothermia is far more efficient than magnetic hyperthermia.

J Control Release 2018 06 21;279:271-281. Epub 2018 Apr 21.

Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot, Paris Cedex 05 75205, France. Electronic address:

Providing appropriate means for heat generation by low intratumoral nanoparticle concentrations is a major challenge for cancer nanotherapy. Here we propose RGD-tagged magnetosomes ([email protected]) as a biogenic, genetically engineered, inorganic platform for multivalent thermal cancer treatment. [email protected] are biomagnetite nanoparticles synthesized by genetically modified magnetotactic bacteria thanks to a translational fusion of the RGD peptide with the magnetosomal protein MamC. [email protected] thus combine the high crystallinity of their magnetite core with efficient surface functionalization. The specific affinity of RGD was first quantified by single-cell magnetophoresis with a variety of cell types, including immune, muscle, endothelial, stem and cancer cells. The highest affinity and cellular uptake was observed with PC3 prostatic and HeLa uterine cancer cells. The efficiency of photothermia and magnetic hyperthermia was then compared on PC3 cells. Unexpectedly, photothermia was far more efficient than magnetic hyperthermia, which was almost totally inhibited by the cellular environment. RGD targeting was then assessed in vivo at tumor site, in mice bearing PC3 tumors. As a result, we demonstrate that targeted magnetic nanoparticles could generate heat on a therapeutic level after systemic administration, but only under laser excitation, and successfully inhibit tumor progression.
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http://dx.doi.org/10.1016/j.jconrel.2018.04.036DOI Listing
June 2018

Dually responsive gold-iron oxide heterodimers: merging stimuli-responsive surface properties with intrinsic inorganic material features.

Nanoscale 2018 Feb;10(8):3930-3944

Istituto Italiano di Tecnologia, via Morego 30, 16145, Genoa, Italy.

We demonstrate a versatile approach for the preparation of dually responsive smart inorganic heterostructures (HSs) with the potential for exploitation in nanomedicine. We utilize Au-FeO dimers as templates for generating smart inorganic HSs with a pH-responsive coating and a thermo-responsive coating attached to iron oxide and gold nanoparticles (NPs), respectively. First, a thiol-modified thermo-responsive (PNIPAAM-co-PEGA) polymer could be selectively attached to the gold domain by ligand exchange. The sequential attachment of a catechol-modified initiator to the iron oxide surface enables the in situ polymerization of a pH-responsive (PDMAEA) polymer. As hereby shown, the presence of the two distinct polymer domains on each NP subdomain enables each side of the HS to be loaded with different agents. Indeed, by a gel electrophoresis experiment we demonstrate the loading of siRNA on the pH-responsive polymer and the loading of Nile Blue dye, used as a drug model molecule, on the thermo-responsive polymer. The smart HSs exhibited good biocompatibility and downregulated GFP production when loaded with anti-GFP siRNA molecules. In addition, an investigation of the magnetic relaxivity times revealed that the high R2 relaxivity values of the HSs suggest their potential as contrast agents in magnetic resonance imaging (MRI) applications.
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http://dx.doi.org/10.1039/c7nr06726gDOI Listing
February 2018

Post-Synthesis Incorporation of ⁶⁴Cu in CuS Nanocrystals to Radiolabel Photothermal Probes: A Feasible Approach for Clinics.

J Am Chem Soc 2015 Dec 25;137(48):15145-51. Epub 2015 Nov 25.

Istituto Italiano di Tecnologia , Via Morego 30, 16163, Genova, Italy.

We report a simple method for the incorporation of Cu(I) or (64)Cu(I) radionuclides in covellite nanocrystals (CuS NCs). After the in situ reduction of Cu(II) or (64)Cu(II) ions by ascorbic acid, their incorporation in PEG-coated CuS NCs takes place at room temperature. In all the reaction steps, the stability of the NCs under physiological conditions was ensured. The copper incorporation reaction could also take place on CuS NCs bearing biotin molecules at their surface, with no detrimental effects on the specific binding affinity of the NCs toward streptavidin after incorporation. At low loading of Cu ions, the strong near-infrared (NIR) absorption band of the starting CuS NCs was essentially preserved, which allowed for efficient plasmonic photothermal therapy. The combined presence in the NCs of (64)Cu ions, well suitable for positron emission tomography, and of free carriers responsible for the NIR absorption, should enable their theranostic use as radiotracers and as photothermal probes in tumor ablation treatments. Moreover, the simplicity of the preparation scheme, which involves the use of radioactive species only as a last step, makes the protocol easily transferable to the clinical practice.
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http://dx.doi.org/10.1021/jacs.5b07973DOI Listing
December 2015

Functionalization of strongly interacting magnetic nanocubes with (thermo)responsive coating and their application in hyperthermia and heat-triggered drug delivery.

ACS Appl Mater Interfaces 2015 May 5;7(19):10132-45. Epub 2015 May 5.

†Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.

Herein, we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermoresponsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR), but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermoresponsive shell is composed of poly(N-isopropylacrylamide-co-polyethylene glycolmethyl ether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.
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http://dx.doi.org/10.1021/am5088117DOI Listing
May 2015

From Binary Cu2S to ternary Cu-In-S and quaternary Cu-In-Zn-S nanocrystals with tunable composition via partial cation exchange.

ACS Nano 2015 Jan 12;9(1):521-31. Epub 2015 Jan 12.

Department of Nanochemistry, Istituto Italiano di Tecnologia , via Morego, 30, 16163 Genova, Italy.

We present an approach for the synthesis of ternary copper indium sulfide (CIS) and quaternary copper indium zinc sulfide (CIZS) nanocrystals (NCs) by means of partial cation exchange with In(3+) and Zn(2+). The approach consists of a sequential three-step synthesis: first, binary Cu2S NCs were synthesized, followed by the homogeneous incorporation of In(3+) by an in situ partial cation-exchange reaction, leading to CIS NCs. In the last step, a second partial exchange was performed where Zn(2+) partially replaced the Cu(+) and In(3+) cations at the surface, creating a ZnS-rich shell with the preservation of the size and shape. By careful tuning reaction parameters (growth and exchange times as well as the initial Cu(+):In(3+):Zn(2+) ratios), control over both the size and composition was achieved. This led to a broad tuning of photoluminescence of the final CIZS NCs, ranging from 880 to 1030 nm without altering the NCs size. Cytotoxicity tests confirmed the biocompatibility of the synthesized CIZS NCs, which opens up opportunities for their application as near-infrared fluorescent markers in the biomedical field.
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http://dx.doi.org/10.1021/nn505786dDOI Listing
January 2015

Subnanometer local temperature probing and remotely controlled drug release based on azo-functionalized iron oxide nanoparticles.

Nano Lett 2013 Jun 9;13(6):2399-406. Epub 2013 May 9.

Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.

Local heating can be produced by iron oxide nanoparticles (IONPs) when exposed to an alternating magnetic field (AMF). To measure the temperature profile at the nanoparticle surface with a subnanometer resolution, here we present a molecular temperature probe based on the thermal decomposition of a thermo-sensitive molecule, namely, azobis[N-(2-carboxyethyl)-2-methylpropionamidine]. Fluoresceineamine (FA) was bound to the azo molecule at the IONP surface functionalized with poly(ethylene glycol) (PEG) spacers of different molecular weights. Significant local heating, with a temperature increase up to 45 °C, was found at distances below 0.5 nm from the surface of the nanoparticle, which decays exponentially with increasing distance. Furthermore, the temperature increase was found to scale linearly with the applied field at all distances. We implemented these findings in an AMF-triggered drug release system in which doxorubicin was covalently linked at different distances from the IONP surface bearing the same thermo-labile azo molecule. We demonstrated the AMF triggered distance-dependent release of the drug in a cytotoxicity assay on KB cancer cells.
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http://dx.doi.org/10.1021/nl400188qDOI Listing
June 2013

Polymer coated inorganic nanoparticles: tailoring the nanocrystal surface for designing nanoprobes with biological implications.

Nanoscale 2012 Jun 10;4(11):3319-34. Epub 2012 May 10.

National Nanotechnology Laboratory of CNR-NANO, via per Arnesano km 5, 73100 Lecce, Italy.

The use of inorganic nanoparticles in biomedicine, in particular in the field of diagnosis and therapy of human diseases, has rapidly grown in the last few decades. Water solubilisation of the nanoparticles, especially for particles synthesized in non-polar solvents, is an essential prerequisite for their biological exploitation. The encapsulation of surfactant coated nanoparticles into polymer shells represents one of the most suitable and most popular methods to make them water soluble. Herein we provide an overview of the amphiphilic polymer molecules used and the efforts undertaken to further tailor the surface of polymer coated nanoparticles with fluorescent dyes, chemical sensor molecules and small or large biomolecules for the preparation of bio-functional nanoprobes. Their biological implications, highlighting limitations and challenges, are also discussed.
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http://dx.doi.org/10.1039/c2nr30271cDOI Listing
June 2012

Magnetic pH-responsive nanogels as multifunctional delivery tools for small interfering RNA (siRNA) molecules and iron oxide nanoparticles (IONPs).

Chem Commun (Camb) 2012 Feb 23;48(18):2400-2. Epub 2012 Jan 23.

Istituto Italiano di Tecnologia, via Morego 30, 161613, Genoa, Italy.

We here exploit pH-responsive nanogels as carriers to deliver functional anti-GFP siRNA and superparamagnetic IONPs to HeLa-GFP cells. The siRNA release via pH-mediated endosomal escape is shown. The IONPs act first as magnetofection agents to boost cellular uptake and then as probes to track the release mechanism by electron microscopy.
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http://dx.doi.org/10.1039/c2cc17223bDOI Listing
February 2012

Magnetic nanocarriers with tunable pH dependence for controlled loading and release of cationic and anionic payloads.

Adv Mater 2011 Dec 18;23(47):5645-50. Epub 2011 Nov 18.

Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.

Superparamagnetic nanocarriers with tunable pH dependence of the surface charge are designed by a simple co-precipitation method. By exploiting electrostatic interactions, cationic or anionic payloads can be adsorbed and desorbed depending on the pH. On three different resulting nanocarrier systems, experiments of loading and release of gold nanoparticles as well as effective siRNA loading and in vitro delivery on human cells are performed.
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http://dx.doi.org/10.1002/adma.201103505DOI Listing
December 2011
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