Francesca Baldelli Bombelli

Politecnico di Milano | Polimi · Department of Chemistry, Materials and Chemical Engineering "Giulio Natta"

Nanoparticle (NP) self-assembly has led to the fabrication of an array of functional nanoscale systems, having diverse architectures and functionalities. In this perspective, we discuss the design and application of NP suprastructures (SPs) characterized by nanoconfined compartments in their self-assembled framework, providing an overview about SP...

In the continuous search to develop multimodal systems with combined diagnostic and therapeutic functions, several efforts have been focused on the development of multifunctional drug delivery systems. Herein we designed, by a covalent approach, a novel class of fluorinated poly(lactic‐co‐glycolic acid) co‐polymers (F‐PLGA) containing an increasing...

Fluorinated hyperbranched polyether copolymers of tuneable composition and architecture were designed and synthesized to develop drug nanocarriers as well as ¹⁹F MRI contrast agents. The performance of these nanomaterials in terms of nanoparticle formation and drug (dexamethasone) loading, as well as ¹⁹F-MRI detectability, was evaluated. These poly...

Alzheimer’s disease (AD) is a serious neuropathology related to the misfolded assembly state of amyloid-beta (Aβ40 and Aβ42) peptides. It has been demonstrated that protein post-translation modifications (PPTMs) of the more hydrophilic N-term moiety of the Aβ peptide affect its aggregation kinetics and interaction with the environment. Considering...

Abstract Here, we demonstrate that introduction of halogen atoms at the tyrosine 10 phenol ring of the DSGYEV sequence derived from the flexible amyloid‐β N‐terminus, promotes its self‐assembly in the solid state. In particular, we report the crystal structures of two halogen‐modified sequences, which we found to be stabilized in the solid state by...

The use of polymeric nanoparticles (NPs) as therapeutics has been steadily increasing over past decades. In vivo imaging of NPs is necessary to advance the therapeutic performance. 19F Magnetic Resonance Imaging (19F MRI) offers multiple advantages for in vivo imaging. However, design of a probe for both biodistribution and degradation has not been...

Halogen bonding (XB) has been shown to be a powerful tool for promoting molecular self-assembly in different fields. The use of XB for noncovalent assembly of inorganic nanoparticles (NP) is, instead, quite limited, considering how extensively other interactions (i.e., electrostatic forces, hydrophobic effect, hydrogen bonding, etc.) have been expl...

A small series of boron‐dipyrromethene (BODIPY) dyes, characterized by the presence of multibranched fluorinated residues, were designed and synthesized. The dyes differ in both the position (para‐perfluoroalkoxy‐substituted phenyl ring or boron functionalization) and number of magnetically equivalent fluorine atoms (27 or 54 fluorine atoms per mol...

In article number 1805046, Jaakko Akola, Marco Maccarini, and co‐workers use neutron reflectometry and molecular dynamics simulations to quantify how the interaction between cationic functionalized gold nanoparticles and model lipid membranes depends on temperature and the lipid charge. The combination of scattering studies and the computational ap...

Understanding the molecular mechanisms governing nanoparticle–membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse‐grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and m...

It is well known that upon injection of nanoparticles (NPs), blood proteins rapidly adhere to their surface, forming a so called protein corona (PC) and leading to sudden changes in size and surface properties of the nanomaterial. It has also been demonstrated that the external PC controls the in vivo fate of the NPs, including aggregation, targeti...

Background MRI with fluorine 19 (19F) probes has shown an ability to track immune cell activity with a specific, stable, and quantitative signal. In addition, the chemical shift differences of selected 19F probes make dual-probe imaging possible. To improve 19F MRI sensitivity for dual-probe imaging, optimal fluorine probes are needed. Purpose To d...

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell‐labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contr...

Peptide-mediated routes to the synthesis of plasmonic nanoparticles have been drawing increasing attention for the development of chiroptically-active nanoscale architectures. However, designing a multifunctional peptide able to drive the formation of structurally defined nanomaterials endowed with specific functionalities is still challenging. In...

Protein-corona formation in body fluids and/or entrapment of nanoparticles in protein matrices (e.g. food and mucus) can hinder the delivery of nanoparticles, irrespective of the route of administration. Here we demonstrate that certain viral nanoparticles (VNPs) can evade the adhesion of a broad panel of macromolecules from several biological mili...

Polyplexes (PX) are soft materials, obtained by blending polycations and nucleic acids, designed for gene delivery applications. While much is known about the transfection properties of PX, their protein corona, the biomolecules interacting with colloids once in a biological environment, represents an underlooked parameter in gene transfection. In...

Cowpea mosaic virus (CPMV) is a plant virus which is being extensively investigated as a drug delivery and vaccine nanocarrier for parenteral administration. However, to date little is known about the suitability of plant-based nanocarriers for oral delivery. In this study, the colloidal (i.e. aggregation), physical (i.e. denaturation) and chemical...

Der Transport fluorierter Wirkstoffe in wässrigen Medien erfordert stabile und in Wasser dispergierbare Träger. In ihrer Zuschrift (DOI: 10.1002/ange.201710230) beschreiben P. Metrangolo und F. Baldelli Bombelli et al. mit fluorierten Goldnanopartikeln gefüllte Suprapartikel, die mit dem pflanzlichen Protein Hydrophobin II überzogen sind und vom Au...

A passion for fluorine. Transport of fluorinated drugs in aqueous environments requires stable, water-dispersible carriers. In their Communication (DOI: 10.1002/anie.201710230), P. Metrangolo and F. Baldelli Bombelli et al. describe a passionfruit-like supraparticle filled with fluorinated gold nanoparticles, which is coated by the vegetable protei...

Perfluorocarbons are omniphobic compounds as a consequence of their unique properties such as, e.g., high electronegativity, low polarizability, high ionization energy, and low surface tension. The possibility of combining such properties with the features of nanoscale materials promoted a recent upsurge in the production of fluorinated nanoparticl...

Fluorophobic-driven assemblies of gold nanomaterials were stabilized into water-dispersible fluorous supraparticles by the film-forming protein hydrophobin HFBII. Our strategy makes use of fluorous nanomaterials of different dimensions to engineer size and inner functionalization of the resulting confined space. The inner fluorous compartments allo...

Fluorophobic-driven assemblies of gold nanomaterials were stabilized into water-dispersible fluorous supraparticles by the film-forming protein hydrophobin HFBII. Our strategy makes use of fluorous nanomaterials of different dimensions to engineer size and inner functionalization of the resulting confined space. The inner fluorous compartments allo...

One of the main hurdles in nanomedicine is the low stability of drug-nanocarrier complexes as well as the drug delivery efficiency in the region-of-interest. Here, we describe the use of the film-forming protein Hydrophobin HFBII to organize dodecanethiol-protected gold nanoparticles (NPs) into well-defined supraparticles (SPs). The obtained SPs ar...

The African clawed frog, Xenopus laevis, has been used as an efficient pre-clinical screening tool to predict drug safety during the early stages of the drug discovery process. X. laevis is a relatively inexpensive model that can be used in whole organism high-throughput assays whilst maintaining a high degree of homology to the higher vertebrate m...

Amyloid peptides yield a plethora of interesting nanostructures though difficult to control. Here we report that depending on the number, position, and nature of the halogen atoms introduced at either one or both phenylalanine benzene rings of the amyloid β peptide-derived core-sequence KLVFF, four different architectures were obtained in a control...

Hypothesis: It is known that nanoparticles (NPs) in a biological fluid are immediately coated by a protein corona (PC), composed of a hard (strongly bounded) and a soft (loosely associated) layers, which represents the real nano-interface interacting with the cellular membrane in vivo. In this regard, supported lipid bilayers (SLB) have extensivel...

The synthesis and self-assembly capabilities of a new halogen-bond donor ligand, 2,3,5,6-tetrafluoro-4-iodophenyl 5-(1,2-dithiolan-3-yl)pentanoate (1), are reported. The crystal structure of ligand (1) and the formation of a cocrystal with 1,2-di(4-pyridyl)ethylene, (1)(2), both show halogen bonds involving the 4- iodotetrafluorobenzene moiety. Lig...

A novel class of superfluorinated and NIR-luminescent gold nanoclusters were obtained starting from a branched thiol, bearing 27 equivalent (19)F atoms per molecule. These unprecedented clusters combine in a unique nanosystem both NIR photoluminescence and (19)F NMR properties, thus representing a promising multimodal platform for bioimaging applic...

Aim: With the rise in production of nanoparticles (NPs) for an ever-increasing number of applications, there is an urgent need to efficiently assess their potential toxicity. We propose a NP hazard assessment protocol that combines mammalian cytotoxicity data with embryonic vertebrate abnormality scoring to determine an overall toxicity index. Re...

In order to control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome-protein corona (PC) aspects. As a powerful tool in these data mining adventure, quantitative structure-activity relationship (QSAR) approach is...

Nanomedicine aims to find novel solutions for urgent biomedical needs. Despite this, one of the most challenging hurdles that nanomedicine faces is to successfully target therapeutic nanoparticles to cells of interest in vivo. As for any biomaterials, once in vivo, nanoparticles can interact with plasma biomolecules, forming new entities for which...

Nanoparticles in physiological environments are known to selectively adsorb proteins and other biomolecules forming a tightly bound biomolecular 'corona' on their surface. Where the exchange times of the proteins are sufficiently long, it is believed that the protein corona constitutes the particle identity in biological milieu. Here we show that p...

Nanoparticles (NPs) in contact with biological fluids are generally coated with environmental proteins, forming a stronger layer of proteins around the NP surface called the hard corona. Protein corona complexes provide the biological identity of the NPs and their isolation and characterization are essential to understand their in vitro and in vivo...

In this study, aqueous dispersions of partially crystalline PVDF nanoparticles (NPs) were obtained employing Hydrophobin (HFB), an amphiphilic film-forming protein able to film hydrophobic surfaces. Dynamic Light Scattering (DLS) and Trasmission Electron Microscopy (TEM) analysis of PVDF-HFBII aqueous dispersions confirmed the HPBII ability to film...

The final fate of nano-scaled drug delivery systems into the body is highly affected by their interaction with proteins in biological fluids (serum, plasma, etc.). Nanocarriers dispersed in biological fluids bear a protein "corona" that covers their surface. Thus, it is extremely important to evaluate the drug release efficiency also in the biologi...

Fluorine magnetic resonance imaging (FMRI) is one of the most promising among those that do not use radioactive nuclides or ionizing radiations. FMRI agents have been grouped in the following paragraphs according to their chemical structure and divided in three broad groups: molecular tracers, polymers, and (hyper) branched derivatives. Undoubtedly...

Clofarabine is a nucleosidic chemotherapeutic approved for the treatment of acute lymphoblastic leukemia, currently undergoing clinical trials for the treatment of solid tumors. Like for many other, a lipid derivatization of this drug improves pharmacokinetics and relieves the heavy side effects. Since the self-assembly pattern can modulate the bio...

19F-MRI offers unique opportunities to image diseases and track cells and therapeutic agents in vivo. Herein we report a superfluorinated molecular probe, herein called PERFECTA, possessing excellent cellular compatibility, and whose spectral properties, relaxation times, and sensitivity are promising for in vivo 19F-MRI applications. The molecule,...

Metastatic melanoma is a highly aggressive malignancy that has traditionally been very difficult to treat. However, after decades of basic research into the signal transduction pathways that promote cancer cell survival, chemoresistance, growth, and crosstalk with the immune system, targeted therapies have now been developed that offer improved sur...

Nanoparticles, after incubation in biological fluids, adsorb several kinds of biomolecules like lipids, sugars and mainly proteins with high affinities for the nanoparticle surface and with long residence time, forming the so-called hard corona. The biological machinery, such as cellular barriers and membrane receptors can directly engage with the...

Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here,...

The application of nanotechnology in medicine signifies one of the most exciting developments in science over the last decade. Even though advancement has been made in nanoparticle engineering in terms of size, shape and surface functionalisation, the behaviour in vivo remains poorly characterised and understood. The potential impact of engineered...

Superparamagnetic iron oxide nanoparticles (SPIONs) have proved their use in many biomedical applications, such as drug delivery, hyperthermia, and MRI (magnetic resonance imaging) contrast agents. Due to their instability in fluids, several surface coatings have been used to both stabilize and tune the properties of these nanoparticles (NPs) accor...

It is now well established that the surface of nanoparticles (NPs) in a biological environment is immediately modified by the adsorption of biomolecules with the formation of a protein corona and it is also accepted that the protein corona, rather than the original nanoparticle surface, defines a new biological identity. Consequently, a methodology...

The endogenous transport mechanisms which occur in living organisms have evolved to allow selective transport and processing operate on a scale of tens of nanometers. This presents the possibility of unprecedented access for engineered nanoscale materials to organs and sub-cellular locations, materials which may in principle be targeted to precise...

Protein adsorption to nanoparticles (NPs) is a key prerequisite to understand NP-cell interactions. While the layer thickness of the protein corona has been well characterized in many cases, the absolute number of bound proteins and their exchange dynamics in body fluids is difficult to assess. Here we measure the number of molecules adsorbed to su...

The significant role of protein nanoparticle interactions in nanomedicine and nanotoxicity is emerging recently through the identification of the nanoparticles (NP) protein (biomolecule) corona. The dynamic layer of proteins and/or other biomolecules adsorbed to the nanoparticle surface determines how a NP interacts with living systems and thereby...

It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of parti...

The paper describes the effect of a low-frequency alternating magnetic field (LF-AMF) on the permeability and release properties of large (LUVs) and giant (GUVs) unilamellar vesicles loaded with citrate coated cobalt ferrite nanoparticles (NPs). The citrate shell allows a high loading of NPs in lipidvesicles without modifying their magnetic propert...

Understanding the impact of nanomaterials on human health will require more detailed knowledge about the protein corona that surrounds nanoparticles in biological environments.

This chapter reports on the design, preparation, and characterization of liposomes decorated with synthetic lipid-oligonucleotide conjugates. Several key parameters should be considered for a successful preparation of these functional nanostructures that can be employed further as building blocks in DNA-directed assembly of nano-objects. These para...

In this work we have studied the effect of a low-frequency alternating magnetic field (LF-AMF) on the permeability of magnetoliposomes, i.e. liposomes including magnetic nanoparticles within their water pool. Large unilamellar liposomes loaded with magnetic cobalt ferrite nanoparticles (CoFe2O4) have been prepared and characterized. Structural char...

We report experimental evidence of the construction of closed pseudo-hexagonal DNA nanostructures grafted onto lipid membranes (supported planar bilayers or liposomes). The anchoring agent is a cholesteryl tetraethylenglycol-18-mer oligonucleotide, which recruits the complementary sequences added in a sequential fashion. A closed rather than an ope...

DNA nanoconstructs are obtained in solution by using six unique 42-mer DNA oligonucleotides, whose sequences have been designed to form a pseudohexagonal structure. The required flexibility is provided by the insertion of two non-base-paired thymines in the middle of each sequence that work as flexible hinges and constitute the corners of the nanos...

The mechanism of DNA strand exchange, performed in vivo by proteins in the RecA family, is, despite extensive studies, still not understood in detail. We are therefore investigating a model system, using the surface of a lipidvesicle, to systematically study the effect of individual parameters on the rate of the strand exchange reaction. DNAoligonu...

DNA monomers and oligomers are currently showing great promise as building blocks for supramolecular arrays that can self-assemble in a fashion preprogrammed by the base pairing code. The design and build-up of hybrid DNA/amphiphilic self-assemblies can expand the range of possible architectures and enhance the selectivity toward a well-specified g...

Predictions on amphiphilic self-assemblies traditionally rely on considerations on molecular shape and charge of the surfactant. In the case of functional surfactants a more sophisticated toolbox becomes necessary to design amphiphiles encoding chemical functionalities that provide additional responsive properties to their self-assemblies. Here we...

Nucleolipid bilayers have been investigated through neutron diffraction, DSC and FTIR techniques. Two nucleolipids, bearing complementary RNA bases, have been chosen to highlight in their mixtures no ideal behaviors ascribable to attractive inetraction of the same selectivity and stoichiometry as in nucleic acids

Through a combination of small angle neutron scattering and static light scattering we have investigated the aqueous self-assembly of 1,2-dilauroyl-sn-glycero-3-phosphatidyl-uridine (DLPU). This phospholipid reproduces on its polar head the chemistry and the charge of an RNA monomer. The results indicate that DLPU forms flexible cylindrical micelle...

We demonstrate that both the rate and yield of DNA strand exchange is significantly enhanced on the surface of positively charged liposomes compared to in bulk solution, using a FRET setup.

Phosphatidyl-nucleosides are a class of functional amphiphiles, where a nucleic acid monomer is conjugated to a lipid skeleton. These derivatives self-organize in aqueous solution as assemblies of various size, shape, and interfacial curvature. This paper presents a comparison of the aggregation behavior of different 1-R,2-R-sn-glycero-3-phosphatid...

Most of the current research on synthetic bilayer membrane-nucleic acid complexes (lipoplexes) is addressed to lipid self-assemblies as nonviral vectors for genetic material. The vast majority of synthetic nonviral vectors so far considered consists of cationic lipid assemblies where DNA binds to cationic liposomes, thanks to charge compensation be...

1,2-Dilauroyl-sn-glycero-3-phosphatidyl-adenosine in 0.1 M phosphate buffer (pH = 7.5) forms worm-like micelles that with ageing of the solution, self-assemble into helical superstructures. Small-angle neutron scattering has shown that dissolution of even small amounts of oil in the hydrophobic cores induces a dramatic structural transition to form...

Aggregates formed from freshly prepared and annealed samples of dilauroyl-phosphatidyl-adenosine, dilauroyl-phosphatidyl-uridine, and their 1:1 mixture have been investigated by dynamic light scattering, cryo-transmission electron microscopy (cryo-TEM) observations, and circular dichroism. The two surfactants differ only for the nucleoside at the p...

Bilayers of palmitoyl-oleoylphosphatidylnucleoside derivatives (1-palmitoyl-2-oleoyl-phosphatidyl-adenosine and 1-palmitoyl-2-oleoyl-phosphatidyl-uridine) were synthesized and investigated in the low-water content regime by a combination of neutron diffraction and Fourier transform infrared linear dichroism (LD-FTIR). Attention was focused on the m...

We report an investigation of the structural properties of dilauroyl-phosphatidyl-uridine wormlike micelles by the combined use of static light scattering and small angle neutron scattering techniques. The q-range covered in the reciprocal space is large enough for a complete structural characterization of micellar aggregates, which can be deduced...

We present an investigation of the aggregation behavior in aqueous solution of two 1,2-dilauroyl-sn-glycero-3-phosphatidylnucleosides (DLPA and DLPU) and of their 1:1 mixture as a function of lipid concentration. Scattering data and Cryo-TEM observation support evidence for elongated aggregates. Two concentration regimes, related to base stacking e...

This contribution concerns a structural investigation of dilauroylphosphonucleoside aggregates in aqueous solutions as a function of ionic strength and surfactant concentration. A micellar growth in the axial direction to form worm-like aggregates is observed as the surfactant concentration is increased, until the system shows a distinct viscoelast...

We report an investigation on the aggregation of 1,2-dilauroyl-sn-glycero-3-phosphatidyluridine (DLPU), a surfactant molecule that merges the self-assembling properties of lecithins with the molecular recognition characteristics of nucleic bases in a phosphate-buffered aqueous solution at physiological pH and as a function of lipid concentration. B...

Much of the current research on synthetic bilayer membrane-nucleic acid complexes (lipoplexes) is fostered by their potential application in biomedical field, with the aim to engineer lipid self-assemblies as non-viral vectors for genetic material. The vast majority of synthetic non-viral vectors consists of cationic lipid assemblies where DNA bind...