Paolo Faraci | Scuola Normale Superiore (original) (raw)

Papers by Paolo Faraci

Biophysical Chemistry, 2019

Several in vitro experiments have highlighted that the Polycomb group protein BMI1 plays a pivota... more Several in vitro experiments have highlighted that the Polycomb group protein BMI1 plays a pivotal role in determining the biological functions of the Polycomb Repressor Complex 1 (PRC1), including its E3-ligase activity towards the Lys 119 of histone H2A to yield ubiquitinated uH2A. The role of BMI1 in the epigenetic activity of PRC1 is particularly relevant in several cancers, particularly Non-Small Cell Lung Cancer (NSCLC). In this study, using indirect immunofluorescence protocols implemented on a confocal microscopy apparatus, we investigated the relationship between BMI1 and uH2A at different resolutions, in cultured (A549) and clinical NSCLC tissues, at the single cell level. In both cases, we observed a linear dependence of uH2A concentration upon BMI1 expression at the single nucleus level, indicating that the association of BMI1 to PRC1, which is needed for E3-ligase activity, occurs linearly in the physiological BMI1 concentration range. Additionally, in the NSCLC cell line model, a minor pool of uH2A may exist in absence of concurrent BMI1 expression, indicating non-exclusive, although predominant, role of BMI1 in the amplification of the E3-ligase activity of PRC1. A pharmacological downregulator of BMI1, PTC-209, was also tested in this context. Finally, the absence of significant colocalization (as measured by the Pearson's coefficient) between BMI1 and uH2A submicron clusters hints to a dynamic model where PRC1 resides transiently at ubiquitination sites. Beside unveiling subtle functional relationships between BMI1 and uH2A, these results also validate the use of uH2A as downstream "reporter" for BMI1 activity at the nuclear level in NSCLC contexts.

Polymer, 2000

The ultrathin films with nanometre control over thickness and multilayered structures of polypyrr... more The ultrathin films with nanometre control over thickness and multilayered structures of polypyrrole (PPY) were manufactured by in-situ self-assembled technique. A controlled thickness of PPY was deposited on polyanion, poly(styrene sulfonate) (PSS) surfaces as a function of time; previously PSS had been deposited on various substrates (glass, mica, indium-tin-oxide coated glass plates). Later, alternate PPY and PSS films were fabricated on such substrates by the layer-by-layer technique. The films were characterized by using UV-visible, electrochemical and Quartz Crystal Microbalance techniques. The resulting morphology of the manufactured films was investigated by Atomic Force and the Scanning Tunneling Microscopies. The electrochemical surveying of self-assembled PPY films in different electrolytic media highlighted the sensor application. Typical supramolecular films of PPY/PSS were found to have conductivity values in the range of 10 Ϫ2-10 Ϫ1 S/cm.

ACS Omega, 2018

Several nanomaterials rely on the passive accumulation in the neoplasm target because of enhanced... more Several nanomaterials rely on the passive accumulation in the neoplasm target because of enhanced permeability and retention effect. On the other hand, directing nanomaterials to the target by employing the targeting agents may lead to a pivotal improvement in the efficacy of the treatment for a number of cancers. However, targeting moieties often lose their functionality upon injection in the bloodstream, leaving questions on their efficiency. Here, we assessed using a significant in vitro 3D model of pancreatic carcinoma the targeting efficiency of passion fruit-like nanoarchitectures (NAs) incorporated with a peptide that can recognize transferrin directly in the medium, thereby modulating protein solvation. NAs are biodegradable ultrasmall-in-nano platforms that combine the most appealing behaviors of noble metal nanomaterials with organism excretion of the building blocks by the renal pathway. Although the confocal images did not illustrate the significant differences in the targeting efficiency of the peptide-modified NAs, an improved internalization was quantitatively observed by inductively coupled plasma-mass spectrometry analysis. Our findings demonstrate that the peptide conjugation of NAs might be considered to enhance their theranostic potentials for this type of neoplasm.

Nanotechnology, 1999

Nanoscale science and technology is today mainly focused on the fabrication of nanodevices. Our a... more Nanoscale science and technology is today mainly focused on the fabrication of nanodevices. Our approach makes use of lithography processes to build the desired nanostructures directly. The fabrication process involves an electron-beam lithography technique to define metallic microstructures onto which nanometre scale patterning is performed using an atomic force microscope (AFM) as a mechanical modification tool. Both direct material removal

Journal of Drug Targeting, doi:10.3109/1061186X.2013.878941

Background: Catechin–dextran conjugates have recently attracted a lot of attention due to their a... more Background: Catechin–dextran conjugates have recently attracted a lot of attention due to their anticancer activity against a range of cancer cells. Magnetic nanoparticles have the ability to concentrate therapeutically important drugs due to their magnetic-spatial control and provide opportunities for targeted drug delivery.

Purpose: Enhancement of the anticancer efficiency of catechin–dextran conjugate by functionalisation with magnetic iron oxide nanoparticles.

Methods: Modification of the coating shell of commercial magnetic nanoparticles (Endorem) composed of dextran with the catechin–dextran conjugate.

Results: Catechin–dextran conjugated with Endorem (Endo–Cat) increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumour cells placed under magnetic field.

Discussion: The conjugation of catechin–dextran with Endorem enhances the anticancer activity of this drug and provides a new strategy for targeted drug delivery on tumour cells driven by magnetic field.

Conclusion: The ability to spatially control the delivery of the catechin–dextran by magnetic field makes it a promising agent for further application in cancer therapy.

Journal of materials chemistry b, Jul 11, 2013

"Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its t... more "Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its therapeutic
action and minimize side effects, it was covalently conjugated to peptide-encapsulated gold nanospheres
by click-chemistry and then photo-released in a controlled fashion by a multiphoton process. Selective
treatment of a chosen region in a 2D layer of U2Os cancer cells is shown by driving photorelease with 561
nm irradiation at mW power. These results show promising directions for the development of practical
applications based on nanocarriers that can ensure drug delivery with high spatial and temporal control."

MRS Proceedings, 2014

ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works i... more ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works in a synergistic way with others could potentially lead to a completely new type of tools for nanomedicine. The development of nanostructures able to release drugs directly within the target after a stimulus can drastically improve the therapeutics efficiency by reducing side effects. Gold nanoparticles offer one of the most suitable platforms for the development of modular nano-devices. On the one hand, their surface properties enable effective coating by peptides containing at least one cysteine, thus yielding stable and non-cytotoxic systems. On the other, their intriguing photophysics, characterized by the surface plasmon resonance, can be exploited for novel excitation schemes. Doxorubicin is a widely used, but toxic, cancer chemotherapeutic agent. In order to localize its therapeutic action while minimizing its side effects, doxorubicin was covalently conjugated to 30 nm peptide-encapsulated gold nanospheres by click-chemistry and then it was photo-released in a controlled fashion through the cleavage of the 1,2,3-triazolic ring by a multiphoton process using 561 nm irradiation at µW power. Selective apoptosis of human osteosarcoma (U2OS) cells was observed only in the irradiated 100x100 micron area in less than six minutes after the stimulus. Notably, the apoptotic effect of doxorubicin was completely inhibited for at least eight hours until its release “on demand” was externally light-triggered.

Nanotechnology, Apr 17, 2000

Abstract. Nanoscale science and technology is today mainly focused on the fabrication of nanodevi... more Abstract. Nanoscale science and technology is today mainly focused on the fabrication of nanodevices. Our approach makes use of lithography processes to build the desired nanostructures directly. The fabrication process involves an electron-beam lithography technique to define metallic microstructures onto which nanometre scale patterning is performed using an atomic force microscope (AFM) as a mechanical modification tool. Both direct material removal and AFM-assisted mask patterning are applied in order to achieve ...

Applied Physics Letters, 1994

Al/Si/GaAs(001) diode structures grown by molecular beam epitaxy were examined as a function of t... more Al/Si/GaAs(001) diode structures grown by molecular beam epitaxy were examined as a function of the thickness of the Si interface layer and the intensity of the As or Al flux employed during Si deposition. We found that Schottky barriers as low as 0.3–0.4 eV (in the presence of a sufficiently high As flux) or as high as 1.0–1.1 eV (in the presence of a sufficiently high Al flux) can be established on n-type GaAs at Si coverages in the submonolayer to monolayer range. We therefore associate the tunability of the barrier height with a Si-induced local interface dipole.

Review of Scientific Instruments, 2000

The present work describes a simple chamber suitable for morphological investigations by implemen... more The present work describes a simple chamber suitable for morphological investigations by implementing the atomic force microscopy (AFM) in controlled experiments. The novelty of our application stems from proposing an open system located in between the expensive, ultra-high-vacuum instruments and those working in air conditions, both available on the market. The former are in fact designed to obtain a detailed inspection of the samples and to develop particular geometries on them, by means of nanolithography or nanomanipulation, while the latter are designed for and used in all the situations in which the environmental conditions do not cause artifacts, problems, or formation of spurious particles on the samples during imaging. We have developed an ad hoc system based on a high-vacuum chamber (up to 10-6 Torr), which allows us to work under controlled-atmosphere conditions. The system, therefore, can be used with most of the samples which suffer from higher pressures, and exploits all the benefits arising from a controlled environment. We have equipped the chamber with an AFM and a sample-holder/mover. An external X-Y-Z motion controller, completely automated, allows the easy positioning of the sample under the sensing cantilever and the consequent relative approach. Experiments with the proposed system are presented, in which the control of environmental conditions during AFM measurements has been investigated with satisfactory results.

Polymer, 2000

The ultrathin films with nanometre control over thickness and multilayered structures of polypyrr... more The ultrathin films with nanometre control over thickness and multilayered structures of polypyrrole (PPY) were manufactured by in-situ self-assembled technique. A controlled thickness of PPY was deposited on polyanion, poly(styrene sulfonate) (PSS) surfaces as a function of time; previously PSS had been deposited on various substrates (glass, mica, indium-tin-oxide coated glass plates). Later, alternate PPY and PSS films were fabricated on such substrates by the layer-by-layer technique. The films were characterized by using UV-visible, electrochemical and Quartz Crystal Microbalance techniques. The resulting morphology of the manufactured films was investigated by Atomic Force and the Scanning Tunneling Microscopies. The electrochemical surveying of self-assembled PPY films in different electrolytic media highlighted the sensor application. Typical supramolecular films of PPY/PSS were found to have conductivity values in the range of 10 Ϫ2 -10 Ϫ1 S/cm. ᭧

Langmuir, 1999

Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead ... more Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead to the formation of layer-by-layer films at different solid surfaces. The prime variables which determine the films formation of poly(styrene sulfonate) (PSS)/polyaniline (PANI) were the polymer charge and ionic strength. The films were deposited by selecting organic/inorganic acid media at pH 2.8. The building up of such multilayer films was characterized by the increment of the adsorbed amount through UV-visible spectroscopy. A linear increase in the absorption magnitude was measured from 1 to 25 bilayers. The uniformity of the PSS/PANI layer-by-layer (LBL) films could be well-maintained, undoping the films in NaOH for obtaining an emeraldine base form of polyaniline. The built-up multilayers were investigated by atomic force microscopy, scanning tunneling microscopy, and cyclic voltammetric and electrical conductivity measurements. The interesting feature of the nearly equal grain size was noticed between 4 and 15 bilayer films of PSS/PANI. The surface roughness was distinguished beyond 15 bilayers of LBL films. The cyclic voltammogram showed the change in the peaks potential value going from 1 to 20 bilayers. The inhomogeneity incorporated inside the films slowed down the electrochemical kinetics in the PSS/ PANI bilayers while going from 1 to 25 bilayer films. The diffusion coefficient (D0) of PSS/PANI 10 bilayers was estimated to be 2 × 10 -8 cm 2 s -1 . Such multilayer films exhibit conductivity in the area of 0.1 S/cm. 10.

Ferrari Aldo Cecchini Marco Serresi Michela Faraci Paolo Pisignano Dario Beltram Fabio Neuronal Polarity Selection By Topography Induced Focal Adhesion Control Biomaterials 31 Pp 4682 94 Oxford Elsevier 10 1016 J Biomaterials 2010 02 032, Mar 1, 2010

Interaction between differentiating neurons and the extracellular environment guides the establis... more Interaction between differentiating neurons and the extracellular environment guides the establishment of cell polarity during nervous system development. Developing neurons read the physical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. In previous works we demonstrated that PC12 cell interaction with nanogratings (alternating lines of ridges and grooves of submicron size) promotes bipolarity and alignment to the substrate topography. Here, we investigate the role of focal adhesions, cell contractility, and actin dynamics in this process. Exploiting nanoimprint lithography techniques and a cyclic olefin copolymer, we engineered biocompatible nanostructured substrates designed for high-resolution live-cell microscopy. Our results reveal that neuronal polarization and contact guidance are based on a geometrical constraint of focal adhesions resulting in an angular modulation of their maturation and persistence. We report on ROCK1/2-myosin-II pathway activity and demonstrate that ROCK-mediated contractility contributes to polarity selection during neuronal differentiation. Importantly, the selection process confined the generation of actinsupported membrane protrusions and the initiation of new neurites at the poles. Maintenance of the established polarity was independent from NGF stimulation. Altogether our results imply that focal adhesions and cell contractility stably link the topographical configuration of the extracellular environment to a corresponding neuronal polarity state.

RSC Advances, 2013

ABSTRACT A laser light polarization visualizer (LPV) is obtainable by the photopolymerization of ... more ABSTRACT A laser light polarization visualizer (LPV) is obtainable by the photopolymerization of a multi-acrylate monomer, initiated by diketones under a single beam nano-pulsed (λ = 532 nm) laser light. The derived light scattering distribution and polymer anisotropy are dependent on the polarization state of the incident-polymerizing beam. By adding a 1-haloalkane to the mixture, the solid angle of the scattered light increases. This phenomenon is dependent on the halogen of the haloalkane.

Applied Physics Letters, 2001

A single-biomolecule optical toggle switch is demonstrated based on a mutated green fluorescent p... more A single-biomolecule optical toggle switch is demonstrated based on a mutated green fluorescent protein (GFP). We have exploited molecular biology techniques to tailor the GFP molecular structure and photophysical properties and to give it optically controlled bistability between two distinct states. We present optical control of the fluorescence dynamics with two laser beams at 476 and 350 nm down to

Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its th... more Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its therapeutic action and minimize side effects, it was covalently conjugated to peptide-encapsulated gold nanospheres by click-chemistry and then photo-released in a controlled fashion by a multiphoton process. Selective treatment of a chosen region in a 2D layer of U2Os cancer cells is shown by driving photorelease with 561 nm irradiation at mW power. These results show promising directions for the development of practical applications based on nanocarriers that can ensure drug delivery with high spatial and temporal control.

MRS Proceedings, 2014

ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works i... more ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works in a synergistic way with others could potentially lead to a completely new type of tools for nanomedicine. The development of nanostructures able to release drugs directly within the target after a stimulus can drastically improve the therapeutics efficiency by reducing side effects. Gold nanoparticles offer one of the most suitable platforms for the development of modular nano-devices. On the one hand, their surface properties enable effective coating by peptides containing at least one cysteine, thus yielding stable and non-cytotoxic systems. On the other, their intriguing photophysics, characterized by the surface plasmon resonance, can be exploited for novel excitation schemes. Doxorubicin is a widely used, but toxic, cancer chemotherapeutic agent. In order to localize its therapeutic action while minimizing its side effects, doxorubicin was covalently conjugated to 30 nm peptide-encapsulated gold nanospheres by click-chemistry and then it was photo-released in a controlled fashion through the cleavage of the 1,2,3-triazolic ring by a multiphoton process using 561 nm irradiation at µW power. Selective apoptosis of human osteosarcoma (U2OS) cells was observed only in the irradiated 100x100 micron area in less than six minutes after the stimulus. Notably, the apoptotic effect of doxorubicin was completely inhibited for at least eight hours until its release “on demand” was externally light-triggered.

Review of Scientific Instruments, 2000

The present work describes a simple chamber suitable for morphological investigations by implemen... more The present work describes a simple chamber suitable for morphological investigations by implementing the atomic force microscopy (AFM) in controlled experiments. The novelty of our application stems from proposing an open system located in between the expensive, ultra-high-vacuum instruments and those working in air conditions, both available on the market. The former are in fact designed to obtain a detailed inspection of the samples and to develop particular geometries on them, by means of nanolithography or nanomanipulation, while the latter are designed for and used in all the situations in which the environmental conditions do not cause artifacts, problems, or formation of spurious particles on the samples during imaging. We have developed an ad hoc system based on a high-vacuum chamber (up to 10-6 Torr), which allows us to work under controlled-atmosphere conditions. The system, therefore, can be used with most of the samples which suffer from higher pressures, and exploits all the benefits arising from a controlled environment. We have equipped the chamber with an AFM and a sample-holder/mover. An external X-Y-Z motion controller, completely automated, allows the easy positioning of the sample under the sensing cantilever and the consequent relative approach. Experiments with the proposed system are presented, in which the control of environmental conditions during AFM measurements has been investigated with satisfactory results.

Langmuir, 1999

Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead ... more Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead to the formation of layer-by-layer films at different solid surfaces. The prime variables which determine the films formation of poly(styrene sulfonate) (PSS)/polyaniline (PANI) were the polymer charge and ionic strength. The films were deposited by selecting organic/inorganic acid media at pH 2.8. The building up of such multilayer films was characterized by the increment of the adsorbed amount through UV-visible spectroscopy. A linear increase in the absorption magnitude was measured from 1 to 25 bilayers. The uniformity of the PSS/PANI layer-by-layer (LBL) films could be well-maintained, undoping the films in NaOH for obtaining an emeraldine base form of polyaniline. The built-up multilayers were investigated by atomic force microscopy, scanning tunneling microscopy, and cyclic voltammetric and electrical conductivity measurements. The interesting feature of the nearly equal grain size was noticed between 4 and 15 bilayer films of PSS/PANI. The surface roughness was distinguished beyond 15 bilayers of LBL films. The cyclic voltammogram showed the change in the peaks potential value going from 1 to 20 bilayers. The inhomogeneity incorporated inside the films slowed down the electrochemical kinetics in the PSS/ PANI bilayers while going from 1 to 25 bilayer films. The diffusion coefficient (D0) of PSS/PANI 10 bilayers was estimated to be 2 × 10 -8 cm 2 s -1 . Such multilayer films exhibit conductivity in the area of 0.1 S/cm. 10.

Biophysical Chemistry, 2019

Several in vitro experiments have highlighted that the Polycomb group protein BMI1 plays a pivota... more Several in vitro experiments have highlighted that the Polycomb group protein BMI1 plays a pivotal role in determining the biological functions of the Polycomb Repressor Complex 1 (PRC1), including its E3-ligase activity towards the Lys 119 of histone H2A to yield ubiquitinated uH2A. The role of BMI1 in the epigenetic activity of PRC1 is particularly relevant in several cancers, particularly Non-Small Cell Lung Cancer (NSCLC). In this study, using indirect immunofluorescence protocols implemented on a confocal microscopy apparatus, we investigated the relationship between BMI1 and uH2A at different resolutions, in cultured (A549) and clinical NSCLC tissues, at the single cell level. In both cases, we observed a linear dependence of uH2A concentration upon BMI1 expression at the single nucleus level, indicating that the association of BMI1 to PRC1, which is needed for E3-ligase activity, occurs linearly in the physiological BMI1 concentration range. Additionally, in the NSCLC cell line model, a minor pool of uH2A may exist in absence of concurrent BMI1 expression, indicating non-exclusive, although predominant, role of BMI1 in the amplification of the E3-ligase activity of PRC1. A pharmacological downregulator of BMI1, PTC-209, was also tested in this context. Finally, the absence of significant colocalization (as measured by the Pearson's coefficient) between BMI1 and uH2A submicron clusters hints to a dynamic model where PRC1 resides transiently at ubiquitination sites. Beside unveiling subtle functional relationships between BMI1 and uH2A, these results also validate the use of uH2A as downstream "reporter" for BMI1 activity at the nuclear level in NSCLC contexts.

Polymer, 2000

The ultrathin films with nanometre control over thickness and multilayered structures of polypyrr... more The ultrathin films with nanometre control over thickness and multilayered structures of polypyrrole (PPY) were manufactured by in-situ self-assembled technique. A controlled thickness of PPY was deposited on polyanion, poly(styrene sulfonate) (PSS) surfaces as a function of time; previously PSS had been deposited on various substrates (glass, mica, indium-tin-oxide coated glass plates). Later, alternate PPY and PSS films were fabricated on such substrates by the layer-by-layer technique. The films were characterized by using UV-visible, electrochemical and Quartz Crystal Microbalance techniques. The resulting morphology of the manufactured films was investigated by Atomic Force and the Scanning Tunneling Microscopies. The electrochemical surveying of self-assembled PPY films in different electrolytic media highlighted the sensor application. Typical supramolecular films of PPY/PSS were found to have conductivity values in the range of 10 Ϫ2-10 Ϫ1 S/cm.

ACS Omega, 2018

Several nanomaterials rely on the passive accumulation in the neoplasm target because of enhanced... more Several nanomaterials rely on the passive accumulation in the neoplasm target because of enhanced permeability and retention effect. On the other hand, directing nanomaterials to the target by employing the targeting agents may lead to a pivotal improvement in the efficacy of the treatment for a number of cancers. However, targeting moieties often lose their functionality upon injection in the bloodstream, leaving questions on their efficiency. Here, we assessed using a significant in vitro 3D model of pancreatic carcinoma the targeting efficiency of passion fruit-like nanoarchitectures (NAs) incorporated with a peptide that can recognize transferrin directly in the medium, thereby modulating protein solvation. NAs are biodegradable ultrasmall-in-nano platforms that combine the most appealing behaviors of noble metal nanomaterials with organism excretion of the building blocks by the renal pathway. Although the confocal images did not illustrate the significant differences in the targeting efficiency of the peptide-modified NAs, an improved internalization was quantitatively observed by inductively coupled plasma-mass spectrometry analysis. Our findings demonstrate that the peptide conjugation of NAs might be considered to enhance their theranostic potentials for this type of neoplasm.

Nanotechnology, 1999

Nanoscale science and technology is today mainly focused on the fabrication of nanodevices. Our a... more Nanoscale science and technology is today mainly focused on the fabrication of nanodevices. Our approach makes use of lithography processes to build the desired nanostructures directly. The fabrication process involves an electron-beam lithography technique to define metallic microstructures onto which nanometre scale patterning is performed using an atomic force microscope (AFM) as a mechanical modification tool. Both direct material removal

Journal of Drug Targeting, doi:10.3109/1061186X.2013.878941

Background: Catechin–dextran conjugates have recently attracted a lot of attention due to their a... more Background: Catechin–dextran conjugates have recently attracted a lot of attention due to their anticancer activity against a range of cancer cells. Magnetic nanoparticles have the ability to concentrate therapeutically important drugs due to their magnetic-spatial control and provide opportunities for targeted drug delivery.

Purpose: Enhancement of the anticancer efficiency of catechin–dextran conjugate by functionalisation with magnetic iron oxide nanoparticles.

Methods: Modification of the coating shell of commercial magnetic nanoparticles (Endorem) composed of dextran with the catechin–dextran conjugate.

Results: Catechin–dextran conjugated with Endorem (Endo–Cat) increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumour cells placed under magnetic field.

Discussion: The conjugation of catechin–dextran with Endorem enhances the anticancer activity of this drug and provides a new strategy for targeted drug delivery on tumour cells driven by magnetic field.

Conclusion: The ability to spatially control the delivery of the catechin–dextran by magnetic field makes it a promising agent for further application in cancer therapy.

Journal of materials chemistry b, Jul 11, 2013

"Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its t... more "Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its therapeutic
action and minimize side effects, it was covalently conjugated to peptide-encapsulated gold nanospheres
by click-chemistry and then photo-released in a controlled fashion by a multiphoton process. Selective
treatment of a chosen region in a 2D layer of U2Os cancer cells is shown by driving photorelease with 561
nm irradiation at mW power. These results show promising directions for the development of practical
applications based on nanocarriers that can ensure drug delivery with high spatial and temporal control."

MRS Proceedings, 2014

ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works i... more ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works in a synergistic way with others could potentially lead to a completely new type of tools for nanomedicine. The development of nanostructures able to release drugs directly within the target after a stimulus can drastically improve the therapeutics efficiency by reducing side effects. Gold nanoparticles offer one of the most suitable platforms for the development of modular nano-devices. On the one hand, their surface properties enable effective coating by peptides containing at least one cysteine, thus yielding stable and non-cytotoxic systems. On the other, their intriguing photophysics, characterized by the surface plasmon resonance, can be exploited for novel excitation schemes. Doxorubicin is a widely used, but toxic, cancer chemotherapeutic agent. In order to localize its therapeutic action while minimizing its side effects, doxorubicin was covalently conjugated to 30 nm peptide-encapsulated gold nanospheres by click-chemistry and then it was photo-released in a controlled fashion through the cleavage of the 1,2,3-triazolic ring by a multiphoton process using 561 nm irradiation at µW power. Selective apoptosis of human osteosarcoma (U2OS) cells was observed only in the irradiated 100x100 micron area in less than six minutes after the stimulus. Notably, the apoptotic effect of doxorubicin was completely inhibited for at least eight hours until its release “on demand” was externally light-triggered.

Nanotechnology, Apr 17, 2000

Abstract. Nanoscale science and technology is today mainly focused on the fabrication of nanodevi... more Abstract. Nanoscale science and technology is today mainly focused on the fabrication of nanodevices. Our approach makes use of lithography processes to build the desired nanostructures directly. The fabrication process involves an electron-beam lithography technique to define metallic microstructures onto which nanometre scale patterning is performed using an atomic force microscope (AFM) as a mechanical modification tool. Both direct material removal and AFM-assisted mask patterning are applied in order to achieve ...

Applied Physics Letters, 1994

Al/Si/GaAs(001) diode structures grown by molecular beam epitaxy were examined as a function of t... more Al/Si/GaAs(001) diode structures grown by molecular beam epitaxy were examined as a function of the thickness of the Si interface layer and the intensity of the As or Al flux employed during Si deposition. We found that Schottky barriers as low as 0.3–0.4 eV (in the presence of a sufficiently high As flux) or as high as 1.0–1.1 eV (in the presence of a sufficiently high Al flux) can be established on n-type GaAs at Si coverages in the submonolayer to monolayer range. We therefore associate the tunability of the barrier height with a Si-induced local interface dipole.

Review of Scientific Instruments, 2000

The present work describes a simple chamber suitable for morphological investigations by implemen... more The present work describes a simple chamber suitable for morphological investigations by implementing the atomic force microscopy (AFM) in controlled experiments. The novelty of our application stems from proposing an open system located in between the expensive, ultra-high-vacuum instruments and those working in air conditions, both available on the market. The former are in fact designed to obtain a detailed inspection of the samples and to develop particular geometries on them, by means of nanolithography or nanomanipulation, while the latter are designed for and used in all the situations in which the environmental conditions do not cause artifacts, problems, or formation of spurious particles on the samples during imaging. We have developed an ad hoc system based on a high-vacuum chamber (up to 10-6 Torr), which allows us to work under controlled-atmosphere conditions. The system, therefore, can be used with most of the samples which suffer from higher pressures, and exploits all the benefits arising from a controlled environment. We have equipped the chamber with an AFM and a sample-holder/mover. An external X-Y-Z motion controller, completely automated, allows the easy positioning of the sample under the sensing cantilever and the consequent relative approach. Experiments with the proposed system are presented, in which the control of environmental conditions during AFM measurements has been investigated with satisfactory results.

Polymer, 2000

The ultrathin films with nanometre control over thickness and multilayered structures of polypyrr... more The ultrathin films with nanometre control over thickness and multilayered structures of polypyrrole (PPY) were manufactured by in-situ self-assembled technique. A controlled thickness of PPY was deposited on polyanion, poly(styrene sulfonate) (PSS) surfaces as a function of time; previously PSS had been deposited on various substrates (glass, mica, indium-tin-oxide coated glass plates). Later, alternate PPY and PSS films were fabricated on such substrates by the layer-by-layer technique. The films were characterized by using UV-visible, electrochemical and Quartz Crystal Microbalance techniques. The resulting morphology of the manufactured films was investigated by Atomic Force and the Scanning Tunneling Microscopies. The electrochemical surveying of self-assembled PPY films in different electrolytic media highlighted the sensor application. Typical supramolecular films of PPY/PSS were found to have conductivity values in the range of 10 Ϫ2 -10 Ϫ1 S/cm. ᭧

Langmuir, 1999

Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead ... more Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead to the formation of layer-by-layer films at different solid surfaces. The prime variables which determine the films formation of poly(styrene sulfonate) (PSS)/polyaniline (PANI) were the polymer charge and ionic strength. The films were deposited by selecting organic/inorganic acid media at pH 2.8. The building up of such multilayer films was characterized by the increment of the adsorbed amount through UV-visible spectroscopy. A linear increase in the absorption magnitude was measured from 1 to 25 bilayers. The uniformity of the PSS/PANI layer-by-layer (LBL) films could be well-maintained, undoping the films in NaOH for obtaining an emeraldine base form of polyaniline. The built-up multilayers were investigated by atomic force microscopy, scanning tunneling microscopy, and cyclic voltammetric and electrical conductivity measurements. The interesting feature of the nearly equal grain size was noticed between 4 and 15 bilayer films of PSS/PANI. The surface roughness was distinguished beyond 15 bilayers of LBL films. The cyclic voltammogram showed the change in the peaks potential value going from 1 to 20 bilayers. The inhomogeneity incorporated inside the films slowed down the electrochemical kinetics in the PSS/ PANI bilayers while going from 1 to 25 bilayer films. The diffusion coefficient (D0) of PSS/PANI 10 bilayers was estimated to be 2 × 10 -8 cm 2 s -1 . Such multilayer films exhibit conductivity in the area of 0.1 S/cm. 10.

Ferrari Aldo Cecchini Marco Serresi Michela Faraci Paolo Pisignano Dario Beltram Fabio Neuronal Polarity Selection By Topography Induced Focal Adhesion Control Biomaterials 31 Pp 4682 94 Oxford Elsevier 10 1016 J Biomaterials 2010 02 032, Mar 1, 2010

Interaction between differentiating neurons and the extracellular environment guides the establis... more Interaction between differentiating neurons and the extracellular environment guides the establishment of cell polarity during nervous system development. Developing neurons read the physical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. In previous works we demonstrated that PC12 cell interaction with nanogratings (alternating lines of ridges and grooves of submicron size) promotes bipolarity and alignment to the substrate topography. Here, we investigate the role of focal adhesions, cell contractility, and actin dynamics in this process. Exploiting nanoimprint lithography techniques and a cyclic olefin copolymer, we engineered biocompatible nanostructured substrates designed for high-resolution live-cell microscopy. Our results reveal that neuronal polarization and contact guidance are based on a geometrical constraint of focal adhesions resulting in an angular modulation of their maturation and persistence. We report on ROCK1/2-myosin-II pathway activity and demonstrate that ROCK-mediated contractility contributes to polarity selection during neuronal differentiation. Importantly, the selection process confined the generation of actinsupported membrane protrusions and the initiation of new neurites at the poles. Maintenance of the established polarity was independent from NGF stimulation. Altogether our results imply that focal adhesions and cell contractility stably link the topographical configuration of the extracellular environment to a corresponding neuronal polarity state.

RSC Advances, 2013

ABSTRACT A laser light polarization visualizer (LPV) is obtainable by the photopolymerization of ... more ABSTRACT A laser light polarization visualizer (LPV) is obtainable by the photopolymerization of a multi-acrylate monomer, initiated by diketones under a single beam nano-pulsed (λ = 532 nm) laser light. The derived light scattering distribution and polymer anisotropy are dependent on the polarization state of the incident-polymerizing beam. By adding a 1-haloalkane to the mixture, the solid angle of the scattered light increases. This phenomenon is dependent on the halogen of the haloalkane.

Applied Physics Letters, 2001

A single-biomolecule optical toggle switch is demonstrated based on a mutated green fluorescent p... more A single-biomolecule optical toggle switch is demonstrated based on a mutated green fluorescent protein (GFP). We have exploited molecular biology techniques to tailor the GFP molecular structure and photophysical properties and to give it optically controlled bistability between two distinct states. We present optical control of the fluorescence dynamics with two laser beams at 476 and 350 nm down to

Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its th... more Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its therapeutic action and minimize side effects, it was covalently conjugated to peptide-encapsulated gold nanospheres by click-chemistry and then photo-released in a controlled fashion by a multiphoton process. Selective treatment of a chosen region in a 2D layer of U2Os cancer cells is shown by driving photorelease with 561 nm irradiation at mW power. These results show promising directions for the development of practical applications based on nanocarriers that can ensure drug delivery with high spatial and temporal control.

MRS Proceedings, 2014

ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works i... more ABSTRACT Nanomaterials engineered in novel multi-modular systems in which every component works in a synergistic way with others could potentially lead to a completely new type of tools for nanomedicine. The development of nanostructures able to release drugs directly within the target after a stimulus can drastically improve the therapeutics efficiency by reducing side effects. Gold nanoparticles offer one of the most suitable platforms for the development of modular nano-devices. On the one hand, their surface properties enable effective coating by peptides containing at least one cysteine, thus yielding stable and non-cytotoxic systems. On the other, their intriguing photophysics, characterized by the surface plasmon resonance, can be exploited for novel excitation schemes. Doxorubicin is a widely used, but toxic, cancer chemotherapeutic agent. In order to localize its therapeutic action while minimizing its side effects, doxorubicin was covalently conjugated to 30 nm peptide-encapsulated gold nanospheres by click-chemistry and then it was photo-released in a controlled fashion through the cleavage of the 1,2,3-triazolic ring by a multiphoton process using 561 nm irradiation at µW power. Selective apoptosis of human osteosarcoma (U2OS) cells was observed only in the irradiated 100x100 micron area in less than six minutes after the stimulus. Notably, the apoptotic effect of doxorubicin was completely inhibited for at least eight hours until its release “on demand” was externally light-triggered.

Review of Scientific Instruments, 2000

The present work describes a simple chamber suitable for morphological investigations by implemen... more The present work describes a simple chamber suitable for morphological investigations by implementing the atomic force microscopy (AFM) in controlled experiments. The novelty of our application stems from proposing an open system located in between the expensive, ultra-high-vacuum instruments and those working in air conditions, both available on the market. The former are in fact designed to obtain a detailed inspection of the samples and to develop particular geometries on them, by means of nanolithography or nanomanipulation, while the latter are designed for and used in all the situations in which the environmental conditions do not cause artifacts, problems, or formation of spurious particles on the samples during imaging. We have developed an ad hoc system based on a high-vacuum chamber (up to 10-6 Torr), which allows us to work under controlled-atmosphere conditions. The system, therefore, can be used with most of the samples which suffer from higher pressures, and exploits all the benefits arising from a controlled environment. We have equipped the chamber with an AFM and a sample-holder/mover. An external X-Y-Z motion controller, completely automated, allows the easy positioning of the sample under the sensing cantilever and the consequent relative approach. Experiments with the proposed system are presented, in which the control of environmental conditions during AFM measurements has been investigated with satisfactory results.

Langmuir, 1999

Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead ... more Sequential addition of a polyanion, poly(styrene sulfonate), and a polycation, polyaniline, lead to the formation of layer-by-layer films at different solid surfaces. The prime variables which determine the films formation of poly(styrene sulfonate) (PSS)/polyaniline (PANI) were the polymer charge and ionic strength. The films were deposited by selecting organic/inorganic acid media at pH 2.8. The building up of such multilayer films was characterized by the increment of the adsorbed amount through UV-visible spectroscopy. A linear increase in the absorption magnitude was measured from 1 to 25 bilayers. The uniformity of the PSS/PANI layer-by-layer (LBL) films could be well-maintained, undoping the films in NaOH for obtaining an emeraldine base form of polyaniline. The built-up multilayers were investigated by atomic force microscopy, scanning tunneling microscopy, and cyclic voltammetric and electrical conductivity measurements. The interesting feature of the nearly equal grain size was noticed between 4 and 15 bilayer films of PSS/PANI. The surface roughness was distinguished beyond 15 bilayers of LBL films. The cyclic voltammogram showed the change in the peaks potential value going from 1 to 20 bilayers. The inhomogeneity incorporated inside the films slowed down the electrochemical kinetics in the PSS/ PANI bilayers while going from 1 to 25 bilayer films. The diffusion coefficient (D0) of PSS/PANI 10 bilayers was estimated to be 2 × 10 -8 cm 2 s -1 . Such multilayer films exhibit conductivity in the area of 0.1 S/cm. 10.