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.

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.

Shape control of soft patchy nanoparticles under confinement.

Molecular building blocks undergoing a hierarchical assembly process form nano-scale objects which can further assemble into supramolecular structures. When the intermediate units have a limited valence in bonding, complex structures with tailored properties can be created. Here, we consider a composite, star-shaped particle made of f diblock copolymer chains uniformly grafted on a spherical colloid and investigate its first self-assembly stage both in the bulk and under lateral confinement. By means of numerical simulations, we show that, in the bulk, this system develops aggregates whose number and size depend on the temperature as well as on the relative ratio of solvophobic monomers. The emerging aggregates are referred to as patches and impart directionality in bonding to the complex particle. We further characterize how we can control, by changing the lateral confinement, the shape of the brush and the patch properties as a function of the distance between the confining walls. We find that the number of the patches can be determined by tuning the degree of confinement imposed on the particle. Finally, we employ a continuum mechanics model, known as the Liquid Drop Model, to gain insight into the elastic properties of the system. This theoretical approach allows to connect the patch properties to the elastic response of the composite particle.

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.

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.

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.

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.

Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials.

INTRODUCTION: To compare the efficacy of abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 in the treatment of castration-resistant, docetaxel-resistant metastatic prostate cancer. METHODS: An indirect comparison of Overall Survival (OS) and time to PSA progression among abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 was performed with a network metaanalysis. OS in the entire population of patients was the primary endpoint. OS in ECOG 0-1/2, BPISF≤ 4/>4, pretreated with 1 or 2 courses of chemotherapy, age≤65/>65 patients, patients with only bone metastases or bone and visceral metastases, and time to PSA progression were the secondary endpoints. An indirect comparison of the Hazard Ratio and the 95% Confidence Interval was performed, assuming an alpha error of 5% as an index of statistical significance. The among-the-trial heterogeneity was assessed using a qualitative methodological and clinical analysis. RESULTS: Four trials were selected. In three trials, the comparator was placebo, in one trial it was mitoxantrone, the effect of which in improving survival was considered negligible. No significant difference in OS among abiraterone acetate, enzalutamide, cabazitaxel and radium 223 was observed in neither the entire population nor all the subgroups of patients. Enzalutamide resulted significantly better than abiraterone acetate, cabazitaxel or radium-223 in time to PSA progression. CONCLUSION: Since no significant difference in efficacy seems to exist between the four therapeutic options in the treatment of castration-resistant, docetaxel-resistant, metastatic prostate cancer, the safety of the treatment, patient's compliance and costs should represent the criteria to guide clinicians' choice in clinical practice.

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.

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.

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.

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.

Spontaneous assembly of a hybrid crystal-liquid phase in inverse patchy colloid systems.

Materials with well-defined architectures are heavily sought after in view of their diverse technological applications. Among the desired target architectures, lamellar phases stand out for their exceptional mechanical and optical features. Here we show that charged colloids, decorated on their poles with two oppositely charged regions possess the unusual ability to spontaneously assemble in different morphologies of (semi-)ordered, layered particle arrangements which maintain their structural stability over a surprisingly large temperature range. This remarkable capacity is related to a characteristic bonding mechanism: stable intra-layer bonds guarantee the formation of planar aggregates, while strong inter-layer bonds favor the stacking of the emerging planar assemblies. These two types of bonds together are responsible for the self-healing processes occurring during the spontaneous assembly. The resulting phases are characterized by parallel, densely packed, particle layers connected by a relatively small number of intra-layer particles. We investigate the properties of the (semi-)ordered phases in terms of static and dynamic correlation functions, focusing in particular on a novel hybrid crystal-liquid phase that prevails at intermediate temperatures where the inter-layer particles form a mobile, fluid phase.

Systemic Immune-Inflammation Index Predicts the Clinical Outcome in Patients with mCRPC Treated with Abiraterone.

Background: A systemic immune-inflammation index (SII) based on neutrophil (N), lymphocyte (L), and platelet (P) counts has shown a prognostic impact in several solid tumors. The aim of this study is to evaluate the prognostic role of SII in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone post docetaxel. Patients and Methods: We retrospectively reviewed consecutive mCRPC patients treated with abiraterone after docetaxel in our Institutions. X-tile 3.6.1 software, cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR) defined as N/L and platelets-to-lymphocyte ratio (PLR) as P/L. Overall survival (OS) and their 95% Confidence Intervals (95% CI) was estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of SII, PLR, and NLR on overall survival (OS) was evaluated by Cox regression analyses and on prostate-specific antigen (PSA) response rates were evaluated by binary logistic regression. Results: A total of 230 mCRPC patients treated abiraterone were included. SII ≥ 535, NLR ≥ 3 and PLR ≥ 210 were considered as elevated levels (high risk groups. The median OS was 17.3 months, 21.8 months in SII < 535 group and 14.7 months in SII ≥ 535 (p < 0.0001). At univariate analysis Eastern Cooperative Oncology Group (ECOG) performance status, previous enzalutamide, visceral metastases, SII, NLR, and PLR predicted OS. In multivariate analysis, ECOG performance status, previous enzalutamide, visceral metastases, SII, and NLR remained significant predictors of OS [hazard ratio (HR) = 5.08, p < 0.0001; HR = 2.12, p = 0.009, HR = 1.77, 95% p = 0.012; HR = 1.80, p = 0.002; and HR = 1.90, p = 0.001, respectively], whereas, PLR showed a borderline ability only (HR = 1.41, p = 0.068). Conclusion: SII and NLR might represent an early and easy prognostic marker in mCRPC patients treated with abiraterone. Further studies are needed to better define their impact and role in these patients.

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.

Phase behaviour of inverse patchy colloids: effect of the model parameters.

The phase behaviour of inverse patchy colloid systems composed of spherical particles with two oppositely charged patches at the poles is investigated by simulation-based thermodynamic integration schemes. The interaction between the particles is derived via a coarse-grained model characterized by three system parameters: the charge imbalance between the bare colloid and the patches, the patch surface extension and the particle interaction range. Starting from a set of parameters for which a stacking of parallel layers is thermodynamically stable, the effect of each of these three parameters on the phase diagram is studied. Our results show that the region of stability of the layered solid phase can be expanded by increasing the charge imbalance and/or by reducing the interaction range. A larger patch size, on the other hand, stabilizes the layered structure with respect to the competing face centered cubic solid at high pressures but destabilizes it with respect to the fluid phase at low pressures. The location of the liquid-vapour critical point in the temperature versus density plane is also investigated: while the charge imbalance and the patch size affect mainly the critical density, a change of the interaction range has a substantial impact also on the critical temperature.

Inverse patchy colloids with small patches: fluid structure and dynamical slowing down.

Inverse patchy colloids (IPCs) differ from conventional patchy particles because their patches repel (rather than attract) each other and attract (rather than repel) the part of the colloidal surface that is free of patches. These particular features occur, e.g. in heterogeneously charged colloidal systems. Here we consider overall neutral IPCs carrying two, relatively small, polar patches. Previous studies of the same model under planar confinement have evidenced the formation of branched, disordered aggregates composed of ring-like structures. We investigate here the bulk behavior of the system via molecular dynamics simulations, focusing on both the structure and the dynamics of the fluid phase in a wide region of the phase diagram. Additionally, the simulation results for the static observables are compared to the Associative Percus Yevick solution of an integral equation approach based on the multi-density Ornstein-Zernike theory. A good agreement between theoretical and numerical quantities is observed even in the region of the phase diagram where the slowing down of the dynamics occurs.

Soft-patchy nanoparticles: modeling and self-organization.

We consider a novel class of patchy particles inspired by polymer-based complex units where the limited valence in bonding is accompanied by soft interactions and incessant fluctuations of the patch positions, possibly leading to reversible modifications of the patch number and size. We introduce a simple model that takes into account the aforementioned features and we focus on the role played by the patch flexibility on the self-organization of our patchy units in the bulk, with particular attention to the connectivity properties and the morphology of the aggregated networks.