Jiwei Cui

One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering

One-Step Coverage Controllable formation of thin films often requires slow deposition conditions or multiple rounds of coating. Ejima et al. (p. 154; see the Perspective by Bentley and Payne) report a simple and versatile method for coating surfaces with thin biocompatible films made from the condensation of Fe3+ ions and a natural polyphenol, tannic acid, from aqueous solutions. Flat surfaces, colloidal particles, and even bacterial cells could be coated, and the coats could subsequently be degraded by changing the pH. Thin adherent films formed from ferric ions and a natural polyphenol, tannic acid, can coat a wide variety of surfaces. [Also see Perspective by Bentley and Payne] The development of facile and versatile strategies for thin-film and particle engineering is of immense scientific interest. However, few methods can conformally coat substrates of different composition, size, shape, and structure. We report the one-step coating of various interfaces using coordination complexes of natural polyphenols and Fe(III) ions. Film formation is initiated by the adsorption of the polyphenol and directed by pH-dependent, multivalent coordination bonding. Aqueous deposition is performed on a range of planar as well as inorganic, organic, and biological particle templates, demonstrating an extremely rapid technique for producing structurally diverse, thin films and capsules that can disassemble. The ease, low cost, and scalability of the assembly process, combined with pH responsiveness and negligible cytotoxicity, makes these films potential candidates for biomedical and environmental applications.

Immobilization and Intracellular Delivery of an Anticancer Drug Using Mussel-Inspired Polydopamine Capsules

We report a facile approach to immobilize pH-cleavable polymer-drug conjugates in mussel-inspired polydopamine (PDA) capsules for intracellular drug delivery. Our design takes advantage of the facile PDA coating to form capsules, the chemical reactivity of PDA films, and the acid-labile groups in polymer side chains for sustained pH-induced drug release. The anticancer drug doxorubicin (Dox) was conjugated to thiolated poly(methacrylic acid) (PMA(SH)) with a pH-cleavable hydrazone bond, and then immobilized in PDA capsules via robust thiol-catechol reactions between the polymer-drug conjugate and capsule walls. The loaded Dox showed limited release at physiological pH but significant release (over 85%) at endosomal/lysosomal pH. Cell viability assays showed that Dox-loaded PDA capsules enhanced the efficacy of eradicating HeLa cancer cells compared with free drug under the same assay conditions. The reported method provides a new platform for the application of stimuli-responsive PDA capsules as drug delivery systems.

Encapsulation of Water‐Insoluble Drugs in Polymer Capsules Prepared Using Mesoporous Silica Templates for Intracellular Drug Delivery

More than 40% of active compounds identifi ed through screening of combinatorial libraries are poorly water-soluble, rendering them unsuitable for further drug development because of diffi culties associated with their delivery using conventional formulation techniques. [ 1 ] Nanoparticles can act as drug carriers for waterinsoluble cargo and this has become an important emerging area of nanotechnology. [ 2 ] As many potent anticancer agents are hydrophobic molecules, the development of nanomaterials for delivering such drugs has received signifi cant attention. Mesoporous silica (MS) particles are attractive as potential drug delivery systems due to their high surface area (up to ∼ 1500 m 2 g − 1 ), controllable pore size ( ∼ 2–50 nm) and pore structure, and tunable size ( ∼ 60 nm − 10 μ m) and morphology. [ 3 ]

Immunological Principles Guiding the Rational Design of Particles for Vaccine Delivery

Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques. Advances in particle engineering now allow highly tunable physicochemical properties of particle-based vaccines, including composition, size, shape, surface characteristics, and degradability. Enhanced collaborative efforts between researchers in immunology and materials science are expected to rise to next-generation vaccines. This process will be significantly aided by a greater understanding of the immunological principles guiding vaccine antigenicity, immunogenicity, and efficacy. With specific emphasis on PRR-targeted adjuvants and particle physicochemical properties, this review aims to provide an overview of the current literature to guide and focus rational particle-based vaccine design efforts.

Emerging methods for the fabrication of polymer capsules.

Hollow polymer capsules are attracting increasing research interest due to their potential application as drug delivery vectors, sensors, biomimetic nano- or multi-compartment reactors and catalysts. Thus, significant effort has been directed toward tuning their size, composition, morphology, and functionality to further their application. In this review, we provide an overview of emerging techniques for the fabrication of polymer capsules, encompassing: self-assembly, layer-by-layer assembly, single-step polymer adsorption, bio-inspired assembly, surface polymerization, and ultrasound assembly. These techniques can be applied to prepare polymer capsules with diverse functionality and physicochemical properties, which may fulfill specific requirements in various areas. In addition, we critically evaluate the challenges associated with the application of polymer capsules in drug delivery systems.

Engineering poly(ethylene glycol) particles for improved biodistribution.

We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.

Preparation of Nano- and Microcapsules by Electrophoretic Polymer Assembly†

Nanoand microcapsules are of significant interest for application in biomedicine, especially in diagnostics and therapeutic delivery. The fabrication of polymer capsules is often accomplished by the particle-mediated assembly of polymer films, whereby films are formed on particles through polymerization or by depositing multiple polymer layers through layer-by-layer (LbL) assembly. In particular, LbL assembly enables the use of particles of various types, shapes, and sizes as templates and enables a suite of polymers with different properties (functionality, responsiveness, and degradability) to be used to engineer the physical, chemical, and biological properties of the capsules. The versatility of LbL assembly with particle templates has led to the development of a range of coated particles and capsules for diverse applications, including drug and vaccine delivery. 4a–f] Despite the significant progress in the field of LbLengineered particles, the film-deposition process typically requires numerous centrifugation and rinse steps to separate the coating material (e.g., polymer) and the particles. Furthermore, it is generally limited to particles either dense and/or large enough for centrifugal sedimentation. Other methods to generate LbL capsules have also been reported: for example, atomization techniques, filter membranes, and microfluidic systems have been used; however, each of these approaches reduces the diversity of the types of particles and polymers that can be employed. These limitations highlight the necessity for the development of alternative rapid and robust approaches for the formation of LbLassembled coatings on particles to generate engineered core– shell particles and capsules. Herein, we report an electrophoretic polymer assembly (EPA) technique for depositing a range of polymers on particles of different sizes. In this approach, electrophoresis is used to generate particles coated with multiple polymer layers and, following core removal, polymer multilayer capsules. An inherent requirement of EPA is the immobilization of particles in a porous hydrogel; in this study, namely, the biologically derived polysaccharide agarose. Agarose has historically been used with electrophoresis to separate biopolymers (e.g., proteins and nucleic acids) because it gelates under ambient conditions, shows low reactivity, is easy to prepare, and has various, tunable pore sizes. In the present system, agarose acts as a “natural immobilizing microfluidic system”. However, we did not use electrophoresis to simply separate free polymer from deposited polymer, but also to deposit the polymers on immobilized particles (Figure 1). This technique reduces handling times, minimizes

Engineering Polymer Hydrogel Nanoparticles for Lymph Node-Targeted Delivery.

The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association in vitro, but dramatically improves their lymphatic drainage in vivo. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.

Modular assembly of superstructures from polyphenol-functionalized building blocks

The organized assembly of particles into superstructures is typically governed by specific molecular interactions or external directing factors associated with the particle building blocks, both of which are particle-dependent. These superstructures are of interest to a variety of fields because of their distinct mechanical, electronic, magnetic and optical properties. Here, we establish a facile route to a diverse range of superstructures based on the polyphenol surface-functionalization of micro- and nanoparticles, nanowires, nanosheets, nanocubes and even cells. This strategy can be used to access a large number of modularly assembled superstructures, including core-satellite, hollow and hierarchically organized supraparticles. Colloidal-probe atomic force microscopy and molecular dynamics simulations provide detailed insights into the role of surface functionalization and how this facilitates superstructure construction. Our work provides a platform for the rapid generation of superstructured assemblies across a wide range of length scales, from nanometres to centimetres.

Super-soft hydrogel particles with tunable elasticity in a microfluidic blood capillary model

Super-soft PEG hydrogel particles with tunable elasticity are prepared via a mesoporous silica templating method. The deformability behavior of these particles, in a microfluidic blood-capillary model, can be tailored to be similar to that of human red blood cells. These results provide a new platform for the design and development of soft hydrogel particles for investigating bio-nano interactions.