Surface Coating of ZIF-8 Nanoparticles with Polyacrylic Acid: A Facile Approach to Enhance Chemical Stability for Biomedical Applications.

Nanoparticles of zeolitic imidazole framework-8 (ZIF-8 NPs), which are the subclass of metal-organic frameworks consisting of Zn ion and 2-methylimidazole, have been identified as promising drug carriers since their large microporous structure is suited for encapsulating hydrophobic drug molecules. However, one of the limitations of ZIF-8 NPs is their low stability in physiological solutions, especially in the presence of water and phosphate anions. These molecules can interact with the coordinatively unsaturated Zn sites at the external surface to induce the degradation of ZIF-8 NPs.

Recent advance in self-assembled polymeric nanomedicines for gaseous signaling molecule delivery.

Gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H S) have recently been recognized as essential signal mediators that regulate diverse physiological and pathological processes in the human body. With the evolution of gaseous signaling molecule biology, their therapeutic applications have attracted growing attention. One of the challenges in translational research of gaseous signaling molecules is the lack of efficient and safe delivery systems.

Functionalization of Framboidal Phenylboronic Acid-Containing Nanoparticles via Aqueous Suzuki-Miyaura Coupling Reactions.

Polymeric nanoparticles with reactive functional groups are an attractive platform for drug carriers that can be conjugated with drugs through a cleavable covalent linkage. Since the required functional groups vary depending on the drug molecule, there is a need for development of a novel post-modification method to introduce different functional groups to polymeric nanoparticles. We recently reported phenylboronic acid (PBA)-containing nanoparticles (BNP) with a unique framboidal morphology created via one-step aqueous dispersion polymerization.

Reactive Oxygen Species-Triggered Hydrogen Sulfide Release and Cancer-Selective Antiproliferative Effect of Anethole Dithiolethione-Containing Polymeric Micelles.

Hydrogen sulfide (H S) is a gaseous signaling molecule in the human body and has attracted attention in cancer therapy due to its regulatory roles in cancer cell proliferation and migration. Accumulating evidence suggests that continuous delivery of H S to cancer cells for extended periods of time suppresses cancer progression. However, one major challenge in therapeutic applications of H S is its controlled delivery.

Photodegradable Hydrogel Interfaces for Bacteria Screening, Selection, and Isolation.

Biologists have long attempted to understand the relationship between phenotype and genotype. To better understand this connection, it is crucial to develop practical technologies that couple microscopic cell screening with cell isolation at high purity for downstream genetic analysis. Here, the use of photodegradable poly(ethylene glycol) hydrogels for screening and isolation of bacteria with unique growth phenotypes from heterogeneous cell populations is described.

Thioether-Based Polymeric Micelles with Fine-Tuned Oxidation Sensitivities for Chemotherapeutic Drug Delivery.

Oxidation-sensitive drug delivery systems (DDSs) have attracted attention due to the potential to improve efficacy and safety of chemotherapeutics. These systems are designed to release the payload in response to oxidative stress conditions, which are associated with many types of cancer. Despite extensive research on the development of oxidation-sensitive DDS, the lack of selectivity toward cancer cells over healthy cells remains a challenge.

Photodegradable Hydrogels for Rapid Screening, Isolation, and Genetic Characterization of Bacteria with Rare Phenotypes.

Screening mutant libraries (MLs) of bacteria for strains with specific phenotypes is often a slow and laborious process that requires assessment of tens of thousands of individual cell colonies after plating and culturing on solid media. In this report, we develop a three-dimensional, photodegradable hydrogel interface designed to dramatically improve the throughput of ML screening by combining high-density cell culture with precision extraction and the recovery of individual, microscale colonies for follow-up genetic and phenotypic characterization. ML populations are first added to a hydrogel precursor solution consisting of polyethylene glycol (PEG) -nitrobenzyl diacrylate and PEG-tetrathiol macromers, where they become encapsulated into 13 μm thick hydrogel layers at a density of 90 cells/mm, enabling parallel monitoring of 2.

Framboidal Nanoparticles Containing a Curcumin-Phenylboronic Acid Complex with Antiangiogenic and Anticancer Activities.

Curcumin (Cur) has a wide range of bioactivities that show potential for the treatment of cancer as well as chronic diseases associated with inflammation and aging. However, the therapeutic efficacy of Cur has been hampered by its rapid degradation under physiological conditions and low aqueous solubility. To address these problems, we prepared Cur-loaded polymeric nanoparticles (CNPs), in which Cur was complexed with phenylboronic acid-containing framboidal nanoparticles (NPs), by simple mixing of Cur and NPs in an aqueous solution.

On Demand Release and Retrieval of Bacteria from Microwell Arrays Using Photodegradable Hydrogel Membranes.

Microwell arrays are important tools for studying single cell behavior and cell-cell interactions, both in microbial and mammalian systems. However, retrieval of cells from microwell arrays with high spatial precision remains a major technical hurdle that prevents follow-up genetic and phenotypic characterization of cells within observed microwells. This work describes a new, material-based approach to grow and retrieve live bacterial cells from small (≥20 μm diameter) microwells in an array using the plant pathogen as a model bacterium.

Data in support of preparation and functionalization of a clickable polycarbonate monolith.

This data article provides supplementary figures to the research article entitled, "Phase separation approach to a reactive polycarbonate monolith for "click" modifications" (Xin et al., Polymer, 2015, doi:10.1016/j.

Polymeric Framboidal Nanoparticles Loaded with a Carbon Monoxide Donor via Phenylboronic Acid-Catechol Complexation.

Carbon monoxide (CO) is an essential gaseous signaling molecule in the human body. Toward the controlled delivery of CO to the target tissues or cells, nanomaterial-based CO donors have attracted growing attention. Here, we present CO-releasing polymeric nanoparticles (CONPs) prepared by simple mixing of phenylboronic acid-containing framboidal nanoparticles with the catechol-bearing CO-donor Ru(CO)3Cl(L-DOPA) via phenylboronic acid-catechol complexation.

Furoxan-Bearing Micelles for Nitric Oxide Delivery.

Furoxans, or 1,2,5-oxadiazole-N-oxides, are a class of nitric oxide (NO)-donating compounds that release NO in response to thiol-containing molecules. In this study, polymeric micelles bearing furoxan moieties are prepared from an amphiphilic block copolymer consisting of a hydrophobic furoxan-bearing block and a hydrophilic poly(N-acryloylmorpholine) block. The block copolymer is prepared using a combination of the reversible addition-fragmentation chain transfer polymerization and the copper-catalyzed Huisgen cycloaddition techniques.

Mannose-displaying fluorescent framboidal nanoparticles containing phenylboronic acid groups as a potential drug carrier for macrophage targeting.

Functional polymeric nanoparticles have been used for various applications in the biomaterials field. Recently, we reported phenylboronic acid-containing nanoparticles (PBA NPs) having an unique framboidal morphology, prepared in a single-step by the aqueous dispersion polymerization of N-acryloyl-3-aminophenylboronic acid (PBAAM) in the presence of poly(ethylene glycol) acrylamide (PEGAM) as a polymerizable dispersant and N,N'-methylenebisacrylamide (MBAM) as a crosslinker. In this study, we prepared mannosylated and fluorescent PBA NPs that could be used for different applications such as drug delivery and bioimaging.

Back Cover: Macromol. Biosci. 11/2015.

Back Cover: The micellar prodrugs of desmethyl anethole dithiolethione (ADT-OH) with different hydrolysis rates prepared from block copolymers having ADT-OH linked via an ester bond using glycine and isoleucine linkers are presented. Micelles having a glycine linker inhibit proliferation of cancer cells. Further details can be found in the article by U.

NMR spectra and electrochemical behavior of catechol-bearing block copolymer micelles.

Here, we provide the NMR spectra and AFM data for antioxidant micelles prepared from amphiphilic PAM-PDA block copolymers composed of a poly(N-acryloyl morpholine) and a redox-active catechol-bearing block with different catechol content. We also provide details of the electrochemical analysis that showed micelles higher catechol content had a similar redox potential with the small catechol compound dopamine, but slowed down the redox reaction (Hasegawa et al., Polymer (in press)).

Hydrolysis-Sensitive Dithiolethione Prodrug Micelles.

Prodrug micelles carrying 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), a compound possessing chemopreventive properties, are prepared from amphiphilic block copolymers linking ADT-OH via an ester bond using glycine (PAM-PGlyADT) and isoleucine linkers (PAM-PIleADT). The release of ADT-OH from the PAM-PIleADT micelles is much slower than the PAM-PGlyADT micelles. The PAM-PGlyADT micelles show comparable toxicity with ADT-OH in different cancer cell lines, whereas the PAM-PIleADT micelles are not toxic up to 400 µM.

6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that suppress effector T cell responses and can reduce the efficacy of cancer immunotherapies. We previously showed that ultra-small polymer nanoparticles efficiently drain to the lymphatics after intradermal injection and target antigen-presenting cells, including Ly6c(hi) Ly6g(-) monocytic MDSCs (Mo-MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra-small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used in the treatment of myelogenous leukemia, with the aim of killing Mo-MDSCs in tumor-bearing mice and thus enhancing T cell-mediated anti-tumor responses.

Pepsin immobilization on an aldehyde-modified polymethacrylate monolith and its application for protein analysis.

Polymer-based monoliths with interconnected porous structure have attracted much attention as a high-performance stationary phase for online digestion liquid chromatography-mass spectrometry (LC-MS) system. In this study, a poly(glycidyl methacrylate-co-methyl methacrylate) (PGM) monolith prepared via thermally induced phase separation (TIPS) was used as a solid support to covalently immobilize pepsin. The PGM monolith was modified with aminoacetal to yield an aldehyde-bearing (PGM-CHO) monolith.

Microscale patterning of hydrogel stiffness through light-triggered uncaging of thiols.

Mammalian cell behavior is strongly influenced by physical and chemical cues originating from the extracellular matrix (ECM). In vivo, ECM signals are displayed in a spatiotemporally complex fashion, often composed as gradients and in concentration profiles that change in time. Most in vitro models to study the role of ECM signals in regulating cell behavior are limited in capturing this microenvironmental complexity, as they are static and homogeneous.

Inhibition of angiogenesis by antioxidant micelles.

Antioxidant micelles capable of scavenging reactive oxygen species (ROS) are prepared from poly(ethylene glycol)-b-poly(dopamine) block copolymers. The micelles inhibit tube formation of human umbilical vein endothelial cells (HUVECs) by scavenging endogenous ROS. Furthermore, the micelles inhibit angiogenesis in the chicken ex ovo chorioallantoic membrane assay.

Preparation of poly(γ-glutamic acid)/hydroxyapatite monolith via biomineralization for bone tissue engineering.

A hybrid monolith of poly(γ-glutamic acid) and hydroxyapatite (PGA/HAp monolith) was prepared via biomineralization and used as a macroporous cell scaffold in bone tissue engineering. The PGA monolith having a bimodal pore size distribution was used as a substrate to induce biomineralization. The PGA/HAp monolith was obtained by immersing the PGA monolith in simulated body fluid.

Design and synthesis of polymeric hydrogen sulfide donors.

Hydrogen sulfide (H2S) is a gaseous signaling molecule that has several important biological functions in the human body. Because of the difficulties of handling H2S gas, small organic compounds that release H2S under physiological conditions have been developed. The observed bioactivities of these H2S donors have generally been directly correlated with their H2S release properties.

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose.

In subunit vaccines, strong CD8(+) T-cell responses are desired, yet they are elusive at reasonable adjuvant doses. We show that targeting adjuvant to the lymph node (LN) via ultrasmall polymeric nanoparticles (NPs), which rapidly drain to the LN after intradermal injection, greatly enhances adjuvant efficacy at low doses. Coupling CpG-B or CpG-C oligonucleotides to NPs led to better dual-targeting of adjuvant and antigen (codelivered on separate NPs) in cross-presenting dendritic cells compared with free adjuvant.

In situ cell manipulation through enzymatic hydrogel photopatterning.

The physicochemical properties of hydrogels can be manipulated in both space and time through the controlled application of a light beam. However, methods for hydrogel photopatterning either fail to maintain the bioactivity of fragile proteins and are thus limited to short peptides, or have been used in hydrogels that often do not support three-dimensional (3D) cell growth. Here, we show that the 3D invasion of primary human mesenchymal stem cells can be spatiotemporally controlled by micropatterning the hydrogel with desired extracellular matrix (ECM) proteins and growth factors.

Preparation of well-defined ibuprofen prodrug micelles by RAFT polymerization.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat acute pain, fever, and inflammation and are being explored in a new indication in cancer. Side effects associated with long-term use of NSAIDs such as gastrointestinal damage and elevated risk of stroke, however, can limit their use and exploration in new indications. Here we report a facile method to prepare well-defined amphiphilic diblock copolymer NSAID prodrugs by direct reversible addition-fragmentation transfer (RAFT) polymerization of the acrylamide derivative of ibuprofen (IBU), a widely used NSAID.