Oriented Linear Self-Assembly of Colloidal Nanocrystals through Regioselective Formation of Hydrogen-Bonded Supramolecular Bridges.

The linear assembly of nanocrystals (NCs) with orientational order presents a significant challenge in the field of colloidal assembly. This study presents an efficient strategy for assembling oleic acid (OAH)-capped, faceted rare earth NCs─such as nanorods, nanoplates, and nanodumbbells─into flexible chain-like superstructures. Remarkably, these NC chains exhibit a high degree of particle orientation even with an interparticle distance reaching up to 15 nm. Central to this oriented assembly method is the facet-selective adsorption of low-molecular-weight polyethylene glycol (PEG), such as PEG-400 (Mn = 400), onto specific facets of NCs. This regioselectivity is achieved by exploiting the lower binding affinity of OAH ligands on the (100) facets of rare earth NCs, enabling facet-specific ligand displacement and subsequent PEG attachment. By adjusting the solvent polarity, the linear assembly of NCs is induced by the solvophobic effect, which simultaneously promotes the formation of hydrogen-bonded PEG supramolecular bridges. These supramolecular bridges effectively connect NCs and exhibit sufficient robustness to maintain the structural integrity of the chains, despite the large interparticle spacing. Notably, even when coassembling different types of NCs, the resulting multicomponent chains still feature highly selective facet-to-facet connections. This work not only introduces a versatile method for fabricating well-aligned linear superstructures but also provides valuable insights into the fundamental principles governing the facet-selective assembly of NCs in solution.

Polyelectrolyte-Mediated Modulation of Spatial Internal Stresses of Hydrogels for Complex 3D Actuators.

Hydrogel actuators with complex 3D initial shapes show numerous important applications, but it remains challenging to fabricate such actuators. This article describes a polyelectrolyte-based strategy for modulating small-scale internal stresses within hydrogels to construct complex actuators with tailored 3D initial shapes. Introducing polyelectrolytes into precursor solutions significantly enhances the volume shrinkage of hydrogel networks during polymerization, allowing us to modulate internal stresses. Photopolymerization of these polyelectrolyte-containing solutions through a mask produces mechanically strong hydrogel sheets with large patterned internal stresses. Consequently, these hydrogel sheets attain complex 3D initial shapes at equilibrium, in contrast to the planar initial configuration of 2D actuators. We demonstrate that these 3D actuators can reversibly transform into other 3D shapes (i.e., 3D-to-3D shape transformations) in response to external stimuli. Additionally, we develop a predictive model based on the Flory-Rehner theory to analyze the polyelectrolyte-mediated shrinking behaviors of hydrogel networks during polymerization, allowing precise modulation of shrinkage and internal stress. This polyelectrolyte-boosted shrinking mechanism paves a route to the fabrication of high-performance 3D hydrogel actuators.

Photo-Induced Self-assembly of Copolymer-Capped Nanoparticles into Colloidal Molecules.

Colloidal molecules (CMs) are precisely defined assemblies of nanoparticles (NPs) that mimic the structure of real molecules, but externally programming the precise self-assembly of CMs is still challenging. In this work, we show that the photo-induced self-assembly of complementary copolymer-capped binary NPs can be precisely controlled to form clustered ABx or linear (AB)y CMs at high yield (x is the coordination number of NP-Bs, and y is the repeating unit number of AB clusters). Under UV light irradiation, photolabile p-methoxyphenacyl groups of copolymers on NP-A*s are converted to carboxyl groups (NP-A), which react with tertiary amines of copolymers on NP-B to trigger the directional NP bonding. The x value of ABx can be precisely controlled between 1 and 3 by varying the irradiation duration and hence the amount of carboxyl groups generated on NP-As. Moreover, when NP-A* and NP-B are irradiated after mixing, the assembly process generates AB clusters or linear (AB)y structures with alternating sequence of the binary NPs. This assembly approach offers a simple yet non-invasive way to externally regulate the formation of various CMs on demand without the need of redesigning the surface chemistry of NPs for use in drug delivery, diagnostics, optoelectronics, and plasmonic devices.

Hierarchically Responsive Alternating Nano-Copolymers with Tailored Interparticle Bonds.

Self-assembly of inorganic nanoparticles (NPs) is an essential tool for constructing structured materials with a wide range of applications. However, achieving ordered assembly structures with externally programmable properties in binary NP systems remains challenging. In this work, we assemble binary inorganic NPs into hierarchically pH-responsive alternating copolymer-like nanostructures in an aqueous medium by engineering the interparticle electrostatic interactions. The polymer-grafted NPs bearing opposite charges are viewed as nanoscale monomers ("nanomers"), and copolymerized into alternating nano-copolymers (ANCPs) driven by the formation of interparticle "bonds" between nanomers. The resulting ANCPs exhibit reversibly responsive "bond" length (i.e., the distance between nanomers) in response to the variation of pH in a range of ~7-10, allowing precise control over the surface plasmon resonance of ANCPs. Moreover, specific interparticle "bonds" can break up at pH≥11, leading to the dis-assembly of ANCPs into molecule-like dimers and trimers. These dimeric and trimeric structures can reassemble to form ANCPs owing to the resuming of interparticle "bonds", when the pH value of the solution changes from 11 to 7. The hierarchically responsive nanostructures may find applications in such as biosensing, optical waveguide, and electronic devices.

Polymer-Tethered Nanoparticles: From Surface Engineering to Directional Self-Assembly.

Current interest in nanoparticle ensembles is motivated by their collective synergetic properties that are distinct from or better than those of individual nanoparticles and their bulk counterparts. These new advanced optical, electronic, magnetic, and catalytic properties can find applications in advanced nanomaterials and functional devices, if control is achieved over nanoparticle organization. Self-assembly offers a cost-efficient approach to produce ensembles of nanoparticles with well-defined and predictable structures. Nanoparticles functionalized with polymer molecules are promising building blocks for self-assembled nanostructures, due to the comparable dimensions of macromolecules and nanoparticles, the ability to synthesize polymers with various compositions, degrees of polymerization, and structures, and the ability of polymers to self-assemble in their own right. Moreover, polymer ligands can endow additional functionalities to nanoparticle assemblies, thus broadening the range of their applications.In this Account, we describe recent progress of our research groups in the development of new strategies for the self-assembly of nanoparticles tethered to macromolecules. At the beginning of our journey, we developed a new approach to patchy nanoparticles and their self-assembly. In a thermodynamically driven strategy, we used poor solvency conditions to induce homopolymer surface segregation in pinned micelles (patches). Patchy nanoparticles underwent self-assembly in a well-defined and controlled manner. Following this work, we overcame the limitation of low yield of the generation of patchy nanoparticles, by using block copolymer ligands. For block copolymer-capped nanoparticles, patch formation and self-assembly were "staged" by using distinct stimuli for each process. We expanded this work to the generation of patchy nanoparticles via dynamic exchange of block copolymer molecules between the nanoparticle surface and micelles in the solution. The scope of our work was further extended to a series of strategies that utilized the change in the configuration of block copolymer ligands during nanoparticle interactions. To this end, we explored the amphiphilicity of block copolymer-tethered nanoparticles and complementary interactions between reactive block copolymer ligands. Both approaches enabled exquisite control over directional and self-limiting self-assembly of complex hierarchical nanostructures. Next, we focused on the self-assembly of chiral nanostructures. To enable this goal, we attached chiral molecules to the surface of nanoparticles and organized these hybrid building blocks in ensembles with excellent chiroptical properties. In summary, our work enables surface engineering of polymer-capped nanoparticles and their controllable and predictable self-assembly. Future research in the field of nanoparticle self-assembly will include the development of effective characterization techniques, the synthesis of new functional polymers, and the development of environmentally responsive self-assembly of polymer-capped nanoparticles for the fabrication of nanomaterials with tailored functionalities.

Vesicular self-assembly of copolymer-grafted nanoparticles with anisotropic shapes.

Plasmonic nanovesicles show broad applications in areas such as cancer theranostics and drug delivery, but the preparation of nanovesicles from shaped nanoparticles remains challenging. This article describes the vesicular self-assembly of shaped nanoparticles, such as gold nanocubes grafted with amphiphilic block copolymers, in selective solvents. The nanocubes assembled within the vesicular membranes exhibit two distinctive packing modes, namely square-like and hexagonal packing, depending on the relative dimensions of the copolymer ligands and nanocubes. The corresponding optical properties of the plasmonic nanovesicles can be tuned by varying the length of the grafted copolymers and the size of the nanocubes. This work provides guidance for the fabrication of functional plasmonic vesicles for applications in catalysis, nanomedicines and optical devices.

Precisely Defining Local Gradients of Stimuli-Responsive Hydrogels for Complex 2D-to-4D Shape Evolutions.

The intellectualization and complication of existing self-shaping materials are limited by the inseparable monotonic relationship between their deformation rate and deformation degree (i.e., a higher deformation rate is accompanied by a high deformation degree). This causes that they can only deform from 2D to 3D states. Here, a simple yet versatile strategy to decouple the monotonic correlation between the deformation rate and deformation degree of self-shaping hydrogels is presented for achieving complex deformations from 2D to temporary 3D to 3D (2D-to-4D). It is demonstrated that when the gradient hydrogels prepared by photopolymerization possess dense polymer networks, the local regions with a high deformation rate can exhibit a low deformation degree. The resulting hydrogels can thus deform in a novel 2D-to-4D mode under external stimuli. During the deformation, they first transform into the temporary shapes induced by the local deformation rate difference, and then transform into the final shapes determined by the local deformation degree difference. Through controlling the ultraviolet irradiation direction and time to precisely program the local gradients of self-shaping hydrogels, they can be designed to produce various unprecedented yet controllable 2D-to-4D shape evolutions on demand, such as transformable origami, sequential gesture actions in finger-guessing games, mobile octopuses, time switch, etc.

Electrostatic Adsorption Behaviors of Charged Polymer-Tethered Nanoparticles on Oppositely Charged Surfaces.

Polymer-grafted hairy nanoparticles (HNPs) that combine the unique properties of inorganic nanoparticles (NPs) and polymers are attractive building blocks for the layer-by-layer assembly of functional hybrid materials, but the adsorption behaviors of HNPs on substrates remain unclear. This article describes a systematic study on the adsorption behaviors of charged polymer-grafted HNPs on oppositely charged substrates in different solvent media via a combination of experiments and simulations. It is shown in simulations that the adsorption process of HNPs is associated with the release of counterions around charged polymers on HNPs, thus resulting in a higher energy barrier of NP adsorption than bare NPs without charged polymer tethers. This energy barrier decreases with decreasing the dielectricity of solvents or ionization degree of grafted polymers or increasing ionic strength of the solution. Furthermore, the theoretical prediction is confirmed in experiments by using a model system of poly(acrylic acid)-grafted silica NPs and poly(diallyldimethylammonium chloride)-modified wafers. The work provides guidance for the electrostatic assembly of HNPs into functional hybrid composites with applications in membranes, optical devices, and biomedicines.

Block-Random Copolymer-Micellization-Mediated Formation of Polymeric Patches on Gold Nanoparticles.

Patchy colloidal nanoparticles are important for a broad range of applications, especially as building blocks for complex and functional structural materials, but the controllable generation of chemical patches on as-synthesized nanoparticles remains a challenge. This article describes a robust strategy for the scalable synthesis of high-quality patchy nanoparticles in high yield and solid content. A simple thermal treatment of a mixture of gold nanoparticles and thiol-terminated block-random copolymers in selected solvents produced a variety of patchy nanoparticles with a controlled morphology and number of polymeric patches (e.g., beanlike patch, one patch, two patches, three patches, multiple patches, and open-configuration patch). We show in experiments and simulations that the dynamic detachment/attachment of copolymers and the exchange of copolymers between the nanoparticle surface and free micelles in the solution-which are dictated by the architecture of copolymers-govern the formation of polymeric patches. This work not only offers an effective approach to patchy nanoparticles but also provides new insights into the phase behaviors of copolymers on nanoscale surfaces.

Warfarin compared with non-vitamin K antagonist oral anticoagulants in subjects with liver disease and atrial fibrillation: A meta-analysis.

INTRODUCTION: Many concerns were raised about the outcome of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease. However, the reported relationship between their efficacy and safety was variable. This meta-analysis was performed to evaluate this relationship. METHODS: A systematic literature search up to July 2020 was performed and six studies included 50 074 subjects with atrial fibrillation and liver disease at the baseline with 32 229 non-vitamin K antagonist oral anticoagulant consumers and 18 920 warfarin consumers. They were reporting relationships between non-vitamin K antagonist oral anticoagulants and warfarin in subjects with atrial fibrillation and liver disease. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in subjects with atrial fibrillation and liver disease subjects using the dichotomous method with a random or fixed-effect model. RESULTS: Non-vitamin K antagonist oral anticoagulants consumption was significantly related to lower all-cause mortality in subjects with atrial fibrillation and liver disease (OR, 0.90; 95% CI, 0.81-0.99, P = .03); lower intracranial haemorrhage (OR, 0.67; 95% CI, 0.55- 0.82, P < .001) and low stroke and system embolism (OR, 0.76; 95% CI, 0.68-0.86, P < .001) compared with warfarin consumption. However, non-vitamin K antagonist oral anticoagulants consumption was not significantly related to lower major bleeding in subjects with atrial fibrillation and liver disease (OR, 0.73; 95% CI, 0.52-1.02, P = .06); and gastrointestinal bleeding (OR, 0.93; 95% CI, 0.58-1.49, P = .77) compared with warfarin consumption. CONCLUSIONS: Based on this meta-analysis, non-vitamin K antagonist oral anticoagulant consumption may have an independent lower risk relationship with all-cause mortality, intracranial haemorrhage, and stroke and system embolism compared with warfarin consumption in subjects with atrial fibrillation and liver disease. This relationship forces us to recommend non-vitamin K antagonist oral anticoagulant use in subjects with atrial fibrillation and liver disease for better outcomes and to avoid any possible complications. Further studies are required.

Polymer-guided assembly of inorganic nanoparticles.

The self-assembly of inorganic nanoparticles is of great importance in realizing their enormous potentials for broad applications due to the advanced collective properties of nanoparticle ensembles. Various molecular ligands (e.g., small molecules, DNAs, proteins, and polymers) have been used to assist the organization of inorganic nanoparticles into functional structures at different hierarchical levels. Among others, polymers are particularly attractive for use in nanoparticle assembly, because of the complex architectures and rich functionalities of assembled structures enabled by polymers. Polymer-guided assembly of nanoparticles has emerged as a powerful route to fabricate functional materials with desired mechanical, optical, electronic or magnetic properties for a broad range of applications such as sensing, nanomedicine, catalysis, energy storage/conversion, data storage, electronics and photonics. In this review article, we summarize recent advances in the polymer-guided self-assembly of inorganic nanoparticles in both bulk thin films and solution, with an emphasis on the role of polymers in the assembly process and functions of resulting nanostructures. Precise control over the location/arrangement, interparticle interaction, and packing of inorganic nanoparticles at various scales are highlighted.

Transformable Honeycomb-Like Nanoassemblies of Carbon Dots for Regulated Multisite Delivery and Enhanced Antitumor Chemoimmunotherapy.

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer-associated fibroblasts (CAFs) responsive honeycomb-like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs-loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.

Polymeric Ligand-Mediated Regioselective Bonding of Plasmonic Nanoplates and Nanospheres.

Nanoparticle (NP) clusters are attractive for many applications, but controllable and regioselective assembly of clusters remains challenging. This communication reports a strategy to precisely assemble Ag nanoplates (NP-As) and Au nanospheres (NP-Bs) grafted with copolymer ligands into defined ABx clusters with controlled coordination number (x) and orientation of the NPs. The directional bonding of shaped NPs relies on the stoichiometric reaction of complementary reactive groups on copolymer ligands. The x value of NP clusters can be tuned from 1 to 4 by varying the number ratio of reactive groups on single NP-Bs to NP-As. The regioselective bonding of nanospheres to the edge or face of a central nanoplate is governed by the steric hindrance of copolymeric ligands on the nanoplate. The clusters exhibit distinctive plasmonic properties that are dependent on the bonding modes of NPs. This study paves a route to fabricating nanostructures with high precision and complexity for applications in plasmonics, catalysis, and sensing.

Shape Complementarity Modulated Self-Assembly of Nanoring and Nanosphere Hetero-nanostructures.

Shape complementarity is of paramount importance in molecular recognition, but has rarely been adopted in the self-assembly of colloidal particles, especially in the case of nanoparticles of different shapes. Here, we demonstrated a simple, yet powerful strategy for fabricating gold nanoring-based heterogeneous nanostructures (AuNR-HNs) with well-defined geometries and high yield. The assembly of various geometries of AuNR-HNs is modulated by the shape complementarity of plasmonic nanorings and nanospheres. We also present experimental evidence of dark quadrupolar ring mode excitation in AuNR-HNs through single-particle optical measurements. Our strategy will be beneficial in the study of nanoparticle assembly, photonic element interaction, and the development of plasmon-based optical devices.

Symmetry-Breaking Synthesis of Multicomponent Nanoparticles.

Multicomponent nanoparticles (MCNs) composed of disparate inorganic colloidal components have attracted great attention from researchers in both the academic and industrial community, because of their unique properties and diverse applications in energy conversion and storage; heterogeneous catalysis; optics and electronics; and biomedical imaging, diagnosis, and therapy. Compared with single-component nanoparticles (NPs), new or advanced properties of MCNs arise from the synergistic effect between their constituent components and the presence of nanoscale interfaces between distinct materials within the particles. Consequently, the spatial arrangement of nanoscale domains of MCNs becomes equally important in property or function control of MCNs as their size, shape, and composition, if not more. In particular, compositionally asymmetric MCNs may outperform their symmetric counterparts in many of their applications. To this end, the seed-mediated growth (SMG) method, which involves depositing a second material onto seed NPs, has been considered as the most common strategy for the synthesis of asymmetric MCNs with desired complexity. In this approach, the control of symmetry breaking during MCN growth is usually achieved by manipulating the growth kinetics or using seed NPs with asymmetric shapes or surfaces. Although great progress has been made in the past decade, there remains a challenge to control the shape, orientation and organization of colloidal components of MCNs with a high yield and reproducibility. Recently, several unconventional methods have been developed as an important addition to the synthetic toolbox for the production of complex MCNs that otherwise may not be readily attainable. This Account summarizes recent advancements on the development of unconventional synthetic strategies for breaking the growth symmetry in the synthesis of asymmetric MCNs. We start with a brief discussion of the achievements and limitations of the conventional strategies for symmetry breaking synthesis. In the subsequent section, we present three unconventional approaches toward symmetry-breaking synthesis of asymmetric MCNs, namely, surface-protected growth, interface-guided growth, and welding-induced synthesis. First, we discuss how commonly used soft agents (e.g., collapsed polymer) and hard agents (e.g., silica) can be asymmetrically coated on seed NPs to template the asymmetric growth of secondary material, generating a broad range of MCNs with complex architectures. The unique features and key factors of this surface-protected synthesis are discussed from the viewpoints of the surface chemistry of seed NPs. We further discuss the use of a solid/liquid or liquid/liquid interface to guide the synthesis of Janus or more complex MCNs through two general mechanisms; that is, selective blocking or impeding the access of precursors to one side of seed NPs and interfacial reaction-enabled generation of asymmetric seeds for further growth. Finally, we discuss a symmetry-breaking method beyond the SMG mechanism, directed welding of as-synthesized single-component NPs. Moreover, we discuss how the unique structural symmetry and compositional arrangement of these MCNs significantly alter the physical and chemical properties of MCNs, thus facilitating their performance in exemplary applications of photocatalysis and electrocatalysis. We finally conclude this Account with a summary of recent progress and our future perspective on the future challenges.

Effects of mindfulness-based cognitive therapy on breast cancer survivors with insomnia: A randomised controlled trial.

OBJECTIVE: We investigated the effects of mindfulness-based cognitive therapy on insomnia (MBCT-I) in breast cancer survivors. METHODS: In total, 136 participants were allocated randomly to a MBCT-I group or a waitlist control (WLC) group. Indicators of insomnia and mindfulness were evaluated using the Insomnia Severity Index, actigraphy and the Five Facet Mindfulness Questionnaire. Data were collected at baseline (T1), post-intervention (T2), 3-month follow-up (T3) and 6-month follow-up (T4) time points. RESULTS: Insomnia severity decreased significantly in the MBCT-I group, compared with the WLC group, at T2, T3 and T4 (all p < .001). We found that 59.6% of the MBCT-I group with moderate and severe insomnia improved to no insomnia and subclinical insomnia at T4 relative to T1, accounting for 7.9% and 55.3%, respectively. Compared with the WLC group, the MBCT-I group improved on actigraphy measures of sleep; they exhibited a pattern of decreased sleep onset latency and waking after sleep onset, as well as increased total sleep time and sleep efficiency. Mindfulness also increased more in the MBCT-I group than in the WLC group at T2, T3 and T4 (all p < .001). CONCLUSIONS: MBCT-I may be an efficacious non-pharmacologic intervention to improve sleep quality in breast cancer survivors.

Alternating Copolymerization of Inorganic Nanoparticles.

Nanoparticle self-assembly has emerged as an indispensable tool in designing structured materials with a wide range of applications, but quantitatively predicting the assembly process and structures still remains challenging. Drawing inspiration from the toolbox of molecular reactions and behaviors is of utmost importance in further advancement of principles and theories for assembling nanoparticles at a length scale orders of magnitude larger. Here we represent a general paradigm for the predictive self-assembly of binary inorganic nanoparticles into linear nanostructures in periodic sequence by expanding the horizon of alternating copolymerization at the molecular level to nanoscale colloidal systems. Nanoparticles grafted with reactive block copolymers are viewed as nanoscale monomers ("nanomers"), and the rapid dimerization of co-nanomers into molecular dipole-like dimers, resembling the preferential formation of dimeric intermediates or charge-transfer complexes from co-monomers in molecular copolymerization, is crucial to the organization of co-nanomers in alternating sequence. We also demonstrate that the classic kinetics and statistics of polycondensation of molecular alternating copolymers (e.g., Nylon-66) can be utilized to quantitatively predict the copolymerization process of nanomers.

Cooperative Assembly of Magneto-Nanovesicles with Tunable Wall Thickness and Permeability for MRI-Guided Drug Delivery.

This article describes the fabrication of nanosized magneto-vesicles (MVs) comprising tunable layers of densely packed superparamagnetic iron oxide nanoparticles (SPIONs) in membranes via cooperative assembly of polymer-tethered SPIONs and free poly(styrene)- b-poly(acrylic acid) (PS- b-PAA). The membrane thickness of MVs could be well controlled from 9.8 to 93.2 nm by varying the weight ratio of PS- b-PAA to SPIONs. The increase in membrane thickness was accompanied by the transition from monolayer MVs, to double-layered MVs and to multilayered MVs (MuMVs). This can be attributed to the variation in the hydrophobic/hydrophilic balance of polymer-grafted SPIONs upon the insertion and binding of PS- b-PAA onto the surface of nanoparticles. Therapeutic agents can be efficiently encapsulated in the hollow cavity of MVs and the release of payload can be tuned by varying the membrane thickness of nanovesicles. Due to the high packing density of SPIONs, the MuMVs showed the highest magnetization and transverse relaxivity rate ( r2) in magnetic resonance imaging (MRI) among these MVs and individual SPIONs. Upon intravenous injection, doxorubicin-loaded MuMVs conjugated with RGD peptides could be effectively enriched at tumor sites due to synergetic effect of magnetic and active targeting. As a result, they exhibited drastically enhanced signal in MRI, improved tumor delivery efficiency of drugs as well as enhanced antitumor efficacy, compared with groups with only magnetic or active targeting strategy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to organs/tissues that are not readily accessible by conventional delivery vehicles.

Anisotropic Self-Assembly of Hairy Inorganic Nanoparticles.

Current interest in functional assemblies of inorganic nanoparticles (NPs) stems from their collective properties and diverse applications ranging from nanomedicines to optically active metamaterials. Coating the surface of NPs with polymers allows for tailoring of the interactions between NPs to assemble them into hybrid nanocomposites with targeted architectures. This class of building blocks is termed "hairy" inorganic NPs (HINPs). Regiospecific attachment of polymers has been used to achieve directional interactions for HINP assembly. However, to date anisotropic surface functionalization of NPs still remains a challenge. This Account provides a review of the recent progress in the self-assembly of isotropically functionalized HINPs in both the condensed state and aqueous solution as well as the applications of assembled structures in such areas as biomedical imaging and therapy. It aims to provide fundamental mechanistic insights into the correlation between structural characteristics and self-assembly behaviors of HINPs, with an emphasis on HINPs made from NPs grafted with linear block copolymer (BCP) brushes. The key to the anisotropic self-assembly of these HINPs is the generation of directional interactions between HINPs by designing the surrounding medium (e.g., polymer matrix) or engineering the surface chemistry of the HINPs. First, HINPs can self-assemble into a variety of 1D, 2D, or 3D nanostructures with a nonisotropic local arrangement of NPs in films. Although a template is not always required, a polymer matrix (BCPs or supramolecules) can be used to assist the assembly of HINPs to form hybrid architectures. The interactions between brushes of neighboring HINPs or between HINPs and the polymer matrix can be modulated by varying the grafting density and length of one or multiple types of polymers on the surface of the NPs. Second, the rational design of deformable brushes of BCP or mixed homopolymer tethers on HINPs enables the anisotropic assembly of HINPs (in analogy to molecular self-assembly) into complex functional structures in selective solvents. It is evidenced that the directional interactions between BCP-grafted NPs arise from the redistribution and conformation change of the long, flexible polymer tethers, while the lateral phase separation of brushes on NP surfaces is responsible for the assembly of HINPs carrying binary immiscible homopolymers. For HINPs decorated with amphiphilic BCP brushes, their self-assembly can produce a variety of hybrid structures, such as vesicles with a monolayer of densely packed NPs in the membranes and with controlled sizes, shapes (e.g., spherical, hemispherical, disklike), and morphologies (e.g., patchy, Janus-like). This strategy allows fine-tuning of the NP organization and collective properties of HINP assemblies, thus facilitating their application in effective cancer imaging, therapy, and drug delivery. We expect that the design and assembly of such HINPs with isotropic functionalization is likely to open up new avenues for the fabrication of new functional nanocomposites and devices because of its simplicity, low cost, and ease of scale-up.