Hierarchical self-assembly of patchy colloidal platelets.

Anisotropy at the level of the inter-particle interaction provides the particles with specific instructions for the self-assembly of target structures. The ability to synthesize non-spherical colloids, together with the possibility of controlling the particle bonding pattern via suitably placed interaction sites, is nowadays enlarging the playing field for materials design. We consider a model of anisotropic colloidal platelets with regular rhombic shape and two attractive sites placed along adjacent edges and we run Monte Carlo simulations in two-dimensions to investigate the two-stage assembly of these units into clusters with well-defined symmetries and, subsequently, into extended lattices. Our focus is on how the site positioning and site-site attraction strength can be tuned to obtain micellar aggregates that are robust enough to successively undergo to a second-stage assembly from sparse clusters into a stable hexagonal lattice.

Design of Patchy Rhombi: From Close-Packed Tilings to Open Lattices.

In the realm of functional materials, the production of two-dimensional structures with tunable porosity is of paramount relevance for many practical applications: surfaces with regular arrays of pores can be used for selective adsorption or immobilization of guest units that are complementary in shape and/or size to the pores, thus achieving, for instance, selective filtering or well-defined responses to external stimuli. The principles that govern the formation of such structures are valid at both the molecular and the colloidal scale. Here we provide simple design directions to combine the anisotropic shape of the building units-either molecules or colloids-and selective directional bonding. Using extensive computer simulations, we show that regular rhombic platelets decorated with attractive and repulsive interaction sites form specific tilings, going smoothly from close-packed arrangements to open lattices. The rationale behind the rich tiling scenario observed can be described in terms of steric incompatibilities, unsatisfied bonding geometries, and interplays between local and long-range order.

A Matter of Size and Placement: Varying the Patch Size of Anisotropic Patchy Colloids.

Non-spherical colloids provided with well-defined bonding sites-often referred to as patches-are increasingly attracting the attention of materials scientists due to their ability to spontaneously assemble into tunable surface structures. The emergence of two-dimensional patterns with well-defined architectures is often controlled by the properties of the self-assembling building blocks, which can be either colloidal particles at the nano- and micro-scale or even molecules and macromolecules. In particular, the interplay between the particle shape and the patch topology gives rise to a plethora of tilings, from close-packed to porous monolayers with pores of tunable shapes and sizes. The control over the resulting surface structures is provided by the directionality of the bonding mechanism, which mostly relies on the selective nature of the patches. In the present contribution, we investigate the effect of the patch size on the assembly of a class of anisotropic patchy colloids-namely, rhombic platelets with four identical patches placed in different arrangements along the particle edges. Larger patches are expected to enhance the bond flexibility, while simultaneously reducing the bond selectivity as the single bond per patch condition-which would guarantee a straightforward mapping between local bonding arrangements and long-range pattern formation-is not always enforced. We find that the non-trivial interplay between the patch size and the patch position can either promote a parallel particle arrangement with respect to a non-parallel bonding scenario or give rise to a variety a bonded patterns, which destroy the order of the tilings. We rationalize the occurrence of these two different regimes in terms of single versus multiple bonds between pairs of particles and/or patches.

Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

PURPOSE: The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. METHODS: We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. RESULTS: We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). CONCLUSIONS: Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

Tuning the order of colloidal monolayers: assembly of heterogeneously charged colloids close to a patterned substrate.

We study the behavior of negatively charged colloids with two positively charged polar caps close to a planar patterned surface. The competition between the different anisotropic components of the particle-particle interaction is able by itself to give rise to a rich assembly scenario: colloids with charged surface patterns already form different crystalline domains when adsorbed to a homogeneously charged substrate. Here we consider substrates composed of alternating (negative/neutral, positive/neutral and positive/negative) parallel stripes and, by means of Monte Carlo simulations, we investigate the ordering of the colloids on changing the number of the stripes. We show that the additional competition between the two different lengths scales characterizing the system (i.e., the particle interaction range and the size of the stripes) gives rise to a plethora of distinct particle arrangements, where some well-defined trends can be observed. By accurately tuning the substrate charged motif it is possible to, e.g., promote specific particle arrangements, disfavor crystalline domains or induce the formation of extended, open clusters.

Molecular dynamics simulations of inverse patchy colloids.

Inverse patchy colloids are patchy particles with differently charged surface regions. In this paper we focus on inverse patchy colloids with two different polar patches and an oppositely charged equatorial belt, and we describe a model and a reliable and efficient numerical algorithm that can be applied to investigate the properties of these particles in molecular dynamics simulations.

Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. RESULTS: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules.

Limited bonding valence, usually accompanied by well-defined directional interactions and selective bonding mechanisms, is nowadays considered among the key ingredients to create complex structures with tailored properties: even though isotropically interacting units already guarantee access to a vast range of functional materials, anisotropic interactions can provide extra instructions to steer the assembly of specific architectures. The anisotropy of effective interactions gives rise to a wealth of self-assembled structures both in the realm of suitably synthesized nano- and micro-sized building blocks and in nature, where the isotropy of interactions is often a zero-th order description of the complicated reality. In this review, we span a vast range of systems characterized by limited bonding valence, from patchy colloids of new generation to polymer-based functionalized nanoparticles, DNA-based systems and proteins, and describe how the interaction patterns of the single building blocks can be designed to tailor the properties of the target final structures.

High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer.

BACKGROUND: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer. METHODS: We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2 vs. 0-1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤ 3). RESULTS: Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101). CONCLUSIONS: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.

Self-assembly of Janus particles under shear.

We investigate the self-assembly of colloidal Janus particles under shear flow by employing hybrid molecular dynamics simulations that explicitly take into account hydrodynamic interactions. Under quiescent conditions, the amphiphilic colloids form spherical micellar aggregates of different sizes, where the solvophobic hemispheres are directed towards the core and the solvophilic caps are exposed to the solvent. When sufficiently strong shear is applied, the micelles disaggregate with a consequent decay of the average cluster size. Nonetheless, we find an intermediate shear rate regime where the balance between rearrangement and dissociation favors the growth of the aggregates. Additionally, our simulations show that clusters composed of either 6 or 13 particles are the most stable towards the shear flow due to their high geometric symmetry. Our findings open up a new range of applications for Janus particles, ranging from biotechnology to sensor systems.

Generalized inverse patchy colloid model.

We generalize the inverse patchy colloid model that was originally developed for heterogeneously charged particles with two identical polar patches and an oppositely charged equator to a model that can have a considerably richer surface pattern. Based on a Debye-Hückel framework, we propose a coarse-grained description of the effective pair interactions that is applicable to particles with an arbitrary patch decoration. We demonstrate the versatility of this approach by applying it to models with (i) two differently charged and/or sized patches, and (ii) three, possibly different patches.

Theoretical and numerical investigations of inverse patchy colloids in the fluid phase.

We investigate the structural and thermodynamic properties of a new class of patchy colloids, referred to as inverse patchy colloids (IPCs) in their fluid phase via both theoretical methods and simulations. IPCs are nano- or micro- meter sized particles with differently charged surface regions. We extend conventional integral equation schemes to this particular class of systems: our approach is based on the so-called multi-density Ornstein-Zernike equation, supplemented with the associative Percus-Yevick approximation (APY). To validate the accuracy of our framework, we compare the obtained results with data extracted from NpT and NVT Monte Carlo simulations. In addition, other theoretical approaches are used to calculate the properties of the system: the reference hypernetted-chain (RHNC) method and the Barker-Henderson thermodynamic perturbation theory. Both APY and RHNC frameworks provide accurate predictions for the pair distribution functions: APY results are in slightly better agreement with MC data, in particular at lower temperatures where the RHNC solution does not converge.

Tunable assembly of heterogeneously charged colloids.

The self-assembly of colloidal particles is a route to designed materials production that combines high flexibility, cost effectiveness, and the opportunity to create ordered structures at length scales ranging from nano- to micrometers. For many practical applications in electronics, photovoltaics, and biomimetic material synthesis, ordered mono- and bilayers are often needed. Here we present a novel and simple way to tune via external parameters the ordering of heterogeneously charged colloids into quasi two-dimensional structures. Depending on the charges of the underlying substrate and of the particles, a rich and versatile assembly scenario takes place, resulting from the complex interplay between directional attractive and repulsive particle-particle and particle-substrate interactions. Upon subtle variations of the relative charge of the system components, emerging via pH modification, reversible changes either from extended aggregates to a monomeric phase or from triangular to square domains are observed.

Chromogranin A is a potential prognostic marker in prostate cancer patients treated with enzalutamide.

BACKGROUND: In this retrospective study, we assessed chromogranin A (CgA) baseline value as a possible factor associated with poor prognosis in metastatic castration-resistant prostate cancer (CRPC). METHODS: Thirty-five patients with metastatic CRPC progressing after docetaxel chemotherapy treated with enzalutamide are subdivided into three groups: serum CgA level was normal when <120 ng/ml (group A, n = 10), within three times the upper normal value (UNV) when between 120 and 360 (group B, n = 17), more than three times the UNV when ≥360 ng/ml (group C, n = 8). RESULTS: No correlation was observed in three groups among CgA baseline values and PSA response rates (RR) (P = 0.4648), whereas a significative difference was associated with median progression-free survival (PFS) and overall survival (OS) among three CgA groups (P = 0.0301 and P = 0.0011, respectively). In the multivariate analysis, PSA RR (nonresponsive vs. responsive) and CgA levels (group 3 vs. groups 1 + 2) were predictors of OS (P = 0.0029 and P = 0.0025, respectively), whereas they only were not significantly correlated with PFS, even had a borderline significance (P = 0.0628 and P = 0.0772, respectively). CONCLUSIONS: In CRPC patients treated with enzalutamide, the evaluation of serum CgA levels could be an useful prognostic factor because of the strong association between CgA value more than three times the UNV and clinical outcome, independently from PSA response.

Phase diagram of inverse patchy colloids assembling into an equilibrium laminar phase.

We numerically study the phase behavior of colloidal particles with two charged patches at the poles and an oppositely charged equatorial belt. Interactions between particles are described using the inverse patchy colloid model, where the term inverse emphasizes the difference with respect to conventional patchy particles: as a consequence of the heterogeneous charge distribution, the patches on the particle surface repel each other, whereas the patches and non-patch regions mutually attract. For the model parameters considered in this work, the system exhibits an unusual equilibrium phase diagram characterized by a broad region where a novel structure composed of parallel colloidal monolayers is stable.

Anisotropic functionalized platelets: percolation, porosity and network properties.

Anisotropic functionalized platelets are able to model the assembly behaviour of molecular systems in two dimensions thanks to the unique combination of steric and bonding constraints. The assembly scenarios can vary from open to close-packed crystals, finite clusters and chains, according to the features of the imposed constraints. In this work, we focus on the assembly of equilibrium networks. These networks can be seen as disordered, porous monolayers and can be of interest for instance in nano-filtration and optical applications. We investigate the formation and properties of two dimensional networks from shape anisotropic colloids functionalized with four patches. We characterize the connectivity properties, the typical local bonding motives, as well as the geometric features of the emerging networks for a large variety of different systems. Our results show that networks of shape anisotropic colloids assemble into highly versatile network topologies, that may be utilized for applications at the nanoscale.

Predicting patchy particle crystals: variable box shape simulations and evolutionary algorithms.

We consider several patchy particle models that have been proposed in literature and we investigate their candidate crystal structures in a systematic way. We compare two different algorithms for predicting crystal structures: (i) an approach based on Monte Carlo simulations in the isobaric-isothermal ensemble and (ii) an optimization technique based on ideas of evolutionary algorithms. We show that the two methods are equally successful and provide consistent results on crystalline phases of patchy particle systems.

Patchy colloids: state of the art and perspectives.

Recently, an increasing experimental effort has been devoted to the synthesis of complex colloidal particles with chemically or physically patterned surfaces and possible specific shapes that are far from spherical. These new colloidal particles with anisotropic interactions are commonly named patchy particles. In this Perspective article, we focus on patchy systems characterized by spherical neutral particles with patchy surfaces. We summarize most of the patchy particle models that have been developed so far and describe how their basic features are connected to the physical systems they are meant to investigate. Patchy models consider particles as hard or soft spheres carrying a finite and small number of attractive sites arranged in precise geometries on the particle's surface. The anisotropy of the interaction and the limited valence in bonding are the salient features determining the collective behavior of such systems. By tuning the number, the interaction parameters and the local arrangements of the patches, it is possible to investigate a wide range of physical phenomena, from different self-assembly processes of proteins, polymers and patchy colloids to the dynamical arrest of gel-like structures. We also draw attention to charged patchy systems: colloidal patchy particles as well as proteins are likely charged, hence the description of the presence of heterogeneously distributed charges on the particle surface is a promising perspective for future investigations.

How patchiness controls the properties of chain-like assemblies of colloidal platelets.

Patchy colloidal platelets with non-spherical shapes have been realized with different materials at length scales ranging from nanometers to microns. While the assembly of these hard shapes tends to maximize edge-to-edge contacts, as soon as a directional attraction is added-by means of, e.g. specific ligands along the particle edges-a competition between shape and bonding anisotropy sets in, giving rise to a complex assembly scenario. Here we focus on a two-dimensional system of patchy rhombi, i.e. colloidal platelets with a regular rhombic shape decorated with bonding sites along their perimeter. Specifically, we consider rhombi with two patches, placed on either opposite or adjacent edges. While for the first particle class only chains can form, for the latter we observe the emergence of either chains or loops, depending on the system parameters. According to the patch positioning-classified in terms of different configurations, topologies and distances from the edge center-we are able to characterize the emerging chain-like assemblies in terms of length, packing abilities, flexibility properties and nematic ordering.